Expert Review: Challenges in management of oligometastatic disease – patient selection is key

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crowd of hands_patient selection concept_oncology news australia_800x500Dr Benjamin Chua, Princess Alexandra Hospital, Brisbane.

The opening sessions of COSA examined paradigms in the management of patients with metastatic disease, and how these are being challenged by the emergence of the ‘oligometastatic’ state.

Dr Bruce Mann introduced the somewhat fluid definition of this state as the presence of ‘limited’ sites of metastases (usually four or fewer).

The goal of ablative therapy for oligometastases is to effect cure or at least durable remission, thereby preventing or delaying initiation of systemic therapy.  Furthermore, for patients with more widespread metastatic disease, Dr Ben Solomon presented the concept of ‘oligo-progressors’ and ‘CNS-only progressors’ with, again, ‘limited’ sites of progressive disease.  It may be appropriate to manage these patients’ sites of progression in isolation, and deliver local rather than systemic therapy to obtain long-term remission.

Dr Norman Laperriere, chair of the CNS and paediatric oncology programs at Princess Margaret Hospital in Toronto, gave an overview to the plenary of the tools now at the disposal of the radiation oncologist to deliver highly accurate, ablative doses by way of intracranial stereotactic radiosurgery (SRS) or stereotactic ablative body radiotherapy (SABR).  For the patient, these techniques also have the advantage of fewer treatment sessions compared to conventional fractionated radiotherapy.  In Australia, a randomised phase II trial by the Trans-Tasman Oncology Group (TROG), SAFRON II, is close to activation, and examines the issue of optimal SABR regimes for lung oligometastatic disease.  Importantly, such multicentre studies assist in driving uptake of new technologies, and in standardisation of practice across departments.

While most ablative therapy for metastatic disease is not supported by prospective trials, Dr Laperriere reminded the audience in a subsequent concurrent session of the long history of prospective research into aggressive local treatment of brain metastases.  Survival improvements have been demonstrated by adding local therapy such as surgery or SRS to whole-brain radiotherapy (WBRT).  The role of WBRT is being questioned because of the lack of demonstrated survival benefits, and potential for late neurocognitive deficits.  Current phase III trials by the National Cancer Institute in the United States are examining the issue of omitting WBRT after surgery or SRS, and importantly, these trials now incorporate robust neurocognitive outcome measures.  In Australia, a randomised phase III study on the role of WBRT following surgery or SRS for up to three melanoma brain metastases is close to completing accrual (TROG 08.05) and will be world-first study in histology-specific management of brain metastases.

laser_radiotherapy concept oncology news australia_800x500Now that we have increasingly effective local therapies, the key practice point for oncologists managing oligometastases is patient selection.  Surgery or radiotherapy for oligometastatic disease are not without potential for significant morbidity for the patient, are often resource-intensive for the health service, and the number of patients with oligometastases will only grow with more effective systemic therapies and improved imaging techniques.

The question of which patients with oligometastases will benefit most, and how their disease will behave after treatment, remains poorly answered.  Dr Michael Hofman presented some eye-opening examples from the nuclear medicine unit at Peter MacCallum Cancer Centre, of rapid disease progression after surgery or SABR for oligometastases, and conversely, examples of spontaneous disease remission or stability despite long periods of observation.  There is clearly great heterogeneity in disease behaviour between patients with oligometastases, and even within disease sites in a single patient.  There may be promise in sophisticated functional imaging techniques, or tumour genomic analysis, to identify patients who may have prolonged disease-free intervals after treatment of oligometastases.  At present, however, we are left to rely largely on clinical parameters such as histology, disease-free interval, number and bulk of metastases.

Clinical judgment and a realistic discussion with the patient remain paramount in planning individualised therapy for the oligometastatic state.

Dr Benjamin Chua is a Radiation Oncology Fellow at the Princess Alexandra Hospital, Brisbane. Read Benjamin’s commentary for OncologyNews on De-escalation approaches in HPV associated oropharyngeal squamous cell carcinoma.

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