Can Interrogation of Tumour Characteristics Lead us to Safely Omit Adjuvant Radiotherapy in Patients with Early Breast Cancer?

Adjuvant radiotherapy after breast-conserving surgery has been an important component of the standard of care for early breast cancer. Improvements in breast cancer care have resulted in a substantial reduction in local relapse rates over recent decades. Although the proportional benefits of adjuvant radiotherapy are similar for different prognostic risk groups of patients, the absolute benefits depend on the risk of relapse and therefore vary considerably between prognostic groups. Radiotherapy is not without risk and for some patients at very low risk of relapse the risks of radiotherapy may outweigh the benefit, leading to potential overtreatment. Randomised controlled trial (RCT) evidence shows that omission of radiotherapy in low risk early breast cancer does not reduce overall survival or increase breast cancer mortality and local recurrences are salvageable. Despite this there has not been a change in practice regarding omission of radiotherapy. The reasons for this may include challenges in patient selection. Recent advances in immunohistochemistry and genomic profiling may improve risk stratification and the development of biomarkers to directed therapies. Several RCTs have quantified the benefit of radiotherapy in reducing local relapse. Where a treatment benefit is known but is considered to be so small not to be clinically relevant then alternatives to RCTs may be considered to answer the question of need. This is because we can assess risk against a fixed 'absolute' boundary rather than needing a randomised comparator. The prospective cohort study is an alternative to the RCT design to answer the question of need for radiotherapy. The feasibility of recruitment into biomarker-directed de-escalation studies will become apparent as more studies open. The challenge is to determine if we are able to accurately risk stratify patients and avoid unnecessary toxicity, thereby tailoring the need for adjuvant breast radiotherapy on an individual patient basis.

Stereotactic body radiotherapy (SBRT) in the management of extracranial oligometastatic (OM) disease.

OBJECTIVE: A review of stereotactic body radiotherapy (SBRT) for oligometastases defined as three or fewer sites of isolated metastatic disease. The aim was to identify local control, overall survival (OS) and progression-free survival (PFS) of patients receiving SBRT for oligometastatic (OM) disease. METHODS: Data were analysed for SBRT delivered between 01 September 2010 and 31 March 2014. End points included local control, PFS, OS and toxicity. RESULTS: 76 patients received SBRT. The median age was 60 years (31-89 years). 44 were male. Median follow-up was 12.3 months (0.2-36.9 months). Major primary tumour sites included colorectal (38%), the breast (18%) and the prostate (12%). The treatment sites included lymph nodes (42%), the bone and spine (29%) and soft tissue (29%). 42% were previously treated with conventional radiotherapy. 45% were disease free after SBRT. 4% had local relapse, 45% had distant relapse, and 6% had local and distant relapse. Local control was 89%. The OS was 84.4% at 1 year and 63.2% at 2 years. PFS was 49.1% at 1 year and 26.2% at 2 years. Toxicities included duodenal ulcer and biliary stricture formation. CONCLUSION: SBRT can achieve durable control of OM lesions and results in minimal radiation-induced morbidity. ADVANCES IN KNOWLEDGE: This cohort is one of the largest reported to date and contributes to the field of SBRT in oligometastases that is emerging as an important research area. It is the only study reported from the UK and uses a uniform technique throughout. The efficacy and low toxicity with durable control of local disease with this approach is shown, setting the foundations for future randomized studies.

Stereotactic body radiotherapy for spinal and bone metastases.

Stereotactic body radiotherapy (SBRT) can deliver high radiation doses to small volumes with very tight margins, which has significant advantages when treating tumours close to the spinal cord or at sites of retreatment. When treating spinal tumours, meticulous quality control is essential with effective immobilisation, as dose gradients at the edge of the spinal cord will be steep and excessive movements can be catastrophic. A range of dose-fractionation schedules have been used from single doses of 15-24 Gy to fractionated schedules delivering 15-35 Gy in three to five fractions. Indications include solitary or up to three vertebral metastases and primary tumours, in particular chordomas or bone sarcomas. Pain relief from metastatic disease is seen in over 80%, with similar rates of objective local control. Local control can be achieved in primary tumours of the spine in up to 95% and similar response rates are seen in non-spinal bone metastases. Toxicity rates are low, even in series that have delivered re-irradiation with myelopathy in <1%, although later vertebral fracture may occur. Further prospective studies are required to formally evaluate patient selection and optimal dose and fractionation alongside an evaluation of cost-effectiveness.

Electrocardiographic abnormalities in a patient with subarachnoid haemorrhage.

A 69-year-old woman presented after collapsing. She denied chest pain, breathlessness or headache. She was afebrile and vital signs were unremarkable. She was confused but the remaining physical examination was unremarkable. Routine blood tests were unremarkable. Cardiac enzymes were raised with a troponin I of 0.54. ECG showed Q waves in leads V1-V3 and widespread T wave inversion in leads II, III, aVF and V1-V6. Acute coronary syndrome (ACS) was suspected and antiplatelet treatment started. The following day her confusion worsened. Further review of the ECG found extensive changes unexplained by occlusion of a single artery suggesting extra-cardiac pathology. An urgent CT head was arranged and revealed subarachnoid haemorrhage. ACS treatment was stopped and she was transferred to neurosurgery where her right posterior communicating artery aneurysm was coiled. Fortunately her recovery was uneventful and she was discharged home with no neurological impairment.

Lyme carditis: a reversible cause of complete atrioventricular block.

A 54-year-old American woman presented with an episode of syncope. This had occurred against a background of several days of dizziness and palpitations. Her medical history included Bell's palsy, which had been diagnosed three weeks earlier. On examination, she had a resting bradycardia of 31 beats per minute and her electrocardiogram demonstrated third-degree atrioventricular (AV) block. She was referred to cardiology for consideration of permanent pacemaker implantation. Given her facial nerve palsy and AV block, a diagnosis of Lyme borreliosis was suspected. Within 48 hours of initiation of ceftriaxone, she reverted to sinus rhythm, albeit with a marked first-degree AV block. Subsequent serology confirmed the diagnosis. Reversible causes of complete AV block should always be considered and appropriate therapy may avoid the need for permanent pacemaker insertion.