Predicting Survival with Brain Metastases in the Stereotactic Radiosurgery Era: are Existing Prognostic Scores Still Relevant? Or Can we do Better?

Predicting survival is essential to tailoring treatment for patients diagnosed with brain metastases. We have evaluated the performance of widely used, validated prognostic scoring systems (Graded Prognostic Assessment and diagnosis-specific Graded Prognostic Assessment) in over 1000 'real-world' patients treated with stereotactic radiosurgery to the brain, selected according to National Health Service commissioning criteria. Survival outcomes from our dataset were consistent with those predicted by the prognostic systems, but with certain cancer subtypes showing a significantly better survival than predicted. Although performance status remains the simplest tool for prediction, total brain tumour volume emerges as an independent prognostic factor, and a new, improved, prognostic scoring system incorporating this has been developed.

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.

Prospective Cohort of Referrals to a Cancer of Unknown Primary Clinic, including Direct Access from Primary Care.

AIMS: The UK National Health Service has well-developed site-specific referral pathways for patients with suspected cancer, but historically there has been inequality of access for patients with suspected Metastatic malignant disease of Unknown primary Origin (MUO). The Brighton cancer of unknown primary (CUP) clinic covers a population of about 650 000. As well as 'in-house' referrals, direct general practitioner referrals are also accepted (since 2015), aiming to shorten the diagnostic pathway and improve patient support. We present data from the first 3 years of activity. MATERIALS AND METHODS: Referrals were screened by an oncologist, ensuring adherence to the strict referral criterion of imaging evidence of a suspected diagnosis of MUO. A standardised data collection form was completed at each clinic appointment by the CUP team. Outcomes were cross-checked against clinic lists, letters and multidisciplinary meeting (MDM) records. A data analysis was carried out of all referrals to the CUP clinic (2015-2018), including general practitioner referrals. RESULTS: In total, 258 patients were seen in the CUP clinic in the first 3 years. The median age was 71 years (range 23-95 years). Source of referral: general practitioner (30%); physician (27%); acute oncology (24%); other MDM (16%); surgeon (3%). A final diagnosis of cancer was made in 83% of referrals, with a primary site identified in 83% of those cancer cases: 19% haematological, 11% lung, 9% urological, 8% upper gastrointestinal, 6% breast, 5% skin, 4% gynaecological, 4% lower gastrointestinal, 0.3% thyroid and 0.3% sarcoma. 10% of referrals remained with a MUO diagnosis (not fit for further investigation) and 7% had confirmed CUP. 17% had a benign diagnosis (of which 56% were general practitioner referrals). Of the general practitioner referrals: 55% were seen in the CUP clinic, 31% did not meet referral criteria and 14% were declined after MDM review of imaging confirmed benign appearances. CONCLUSION: The development of direct general practitioner referrals to CUP clinics nationally should be encouraged (as supported by the National Institute for Health and Care Excellence) - they are feasible and manageable within a tertiary CUP clinic, resulting in high rates of cancer diagnoses, with attendant early support from specialist nursing teams and oncological review.

Treatment of recurrent head and neck cancer: re-irradiation or chemotherapy?

For most patients with head and neck cancer, locoregional disease recurrence carries an extremely poor prognosis and has severe adverse effects on quality of life. Only a few patients are suitable for salvage surgery and, even in selected cases, the success rate is low. Most patients are managed by supportive palliative care, or with palliative chemotherapy. In the UK, re-irradiation is rarely used because of concerns about treatment-related toxicity and lack of efficacy. Despite this, a significant body of evidence suggests that re-irradiation may have a higher probability of achieving local control than other treatments. In this review, we discuss the use of re-irradiation in patients with locally recurrent head and neck cancer, and present the pertinent data.

Radiotherapy planning in high-grade gliomas: a survey of current UK practice.

AIMS: Primary brain tumours in adults are rare, with high-grade gliomas (HGG) being the most common and most aggressive type. The clinical management of rare tumours such as HGG can be heterogeneous across different cancer centres. The aim of this survey was to determine current UK practice in the primary management of HGG, particularly in light of the improved outcomes reported recently. MATERIALS AND METHODS: In February 2009, a questionnaire was sent to 71 consultant clinical oncologists in the UK who were reported to have a neuro-oncology practice. Questions focussed on the radiotherapeutic management of HGG. RESULTS: In total, 46/71 (65%) completed questionnaires were returned; 31/46 (67%) routinely used magnetic resonance imaging/computed tomography fusion for radiotherapy planning; 34/36 (94%) routinely prescribed 60Gy in 30 fractions in a single phase; 7/36 (19%) would consider 54-55Gy in 30 fractions in selected clinical scenarios; 42/46 (91%) defined the planning target volume (PTV) as the gross tumour volume (GTV)+2-3cm margin and 42/46 (91%) outlined at least one 'organ at risk' (OAR). Accepted tolerance doses varied considerably, e.g. retina range: 30-54Gy. Sixty-four per cent of clinicians (27/42) compromise the PTV and 30% (14/42) the GTV in order to keep OARs within preset tolerances. Nearly one-third (14/42) involve the patient in this decision-making process, e.g. weighing up the risk of late toxicity with the risks of reducing the dose to the PTV. CONCLUSION: The results of this survey show areas of strong agreement as well as areas of variation in clinical practice of aspects of treatment planning for HGG between UK neuro-oncologists.