Tumour bulk shouldn't be relied on as a marker of prognosis, Australian researchers say.
Tumour bulk is useful in the prognosis of some – but not all – lymphoma tumours, Australian researchers say in research that overturns the reliance on bulk as a marker of prognosis.
“The presence, or absence of bulk, and its definition are fraught with high variation in the contributing factors,” the researchers said in Haematologica.
“Thus, determining the optimal definition of disease bulk for each subtype, the associations with underlying biology and evaluating the utility of this metric in the modern PET era, are priorities for future research.”
The study included 5090 adult lymphoma patients from Australian and New Zealand registries, in which tumour bulk was defined as greater than 5cm. The researchers said 88% of participants had information on the presence of bulk.
The researchers analysed the influence of bulk on outcomes and treatment decisions in diffuse large B-cell (DLBCL), follicular, marginal zone, T-cell, Hodgkin and Burkitt lymphoma (BL).
“Patients with bulk were more likely to receive systemic chemotherapy alone, and less likely to have localised treatment alone (radiotherapy and/or surgery), compared to those without bulk,” they said.
The researchers found that bulk was associated with inferior overall survival in diffuse large B-cell patients and superior survival in Hodgkin patients.
“Exploratory analysis using disease-specific bulk definitions from clinicians practising in Australia and New Zealand showed inferior progression-free survival in DLBCL (bulk >7.5cm) and OS [overall survival] in BL patients (bulk >10cm), but not other subtypes.
“We demonstrated real-world evidence of management heterogeneity for patients with bulk, with potential prognostic implications. International standardisation of the definition of bulk is urged for uniform utility in PET-based and molecular prognostication across clinical studies.”
Lead author and medical oncologist Professor Eliza Hawkes said they found that the size of tumour bulk may be useful in prognostication in some lymphoma subtypes, but not all.
“And more importantly, different definitions of bulk in terms of the size of the tumour apply to different lymphoma subtypes,” she told Oncology Republic.
“But overall, bulk is less useful than originally thought,” said Professor Hawkes, chief clinical research officer and lymphoma lead at the Olivia Newton John Cancer Research Institute at Austin Health.
“Therefore, reliance on bulk as a marker of prognosis should be exchanged for newer prognostic markers.”
Professor Hawkes said more analyses were needed by other large datasets internationally to find the optimal cut-off to predict disease prognosis.
“Our data demonstrate that the oncology community needs to re-evaluate the use of tumour bulk as a decision-marking tool in lymphoma patients and incorporate other imaging technology in routine clinical care rather than using single-dimension measures of an individual tumour lesion ‘bulk’ to do so.”
Professor Hawkes said tumour bulk – the size or volume of a lymphoma mass, usually the largest – was typically measured by the largest diameter of a single lesion on scans such as CT, or previously, X-ray.
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“Historically, it has been considered a key prognostic factor in some lymphoma subtypes, with larger bulk associated with poorer outcomes. It influenced staging, risk stratification, and decisions to commence treatment and intensity of the regimens.”
Patients were previously thought to have worse treatment outcomes if they had a “bulky” tumour at diagnosis, Professor Hawkes said.
“Many were automatically treated with radiotherapy after chemotherapy, or with more intensive therapy due to the presence of ‘bulk’.”
But advances in artificial intelligence and imaging techniques can more accurately visualise and provide digital tools to understand tumour biology and assess treatment response, Professor Hawkes said.
The “activity” of a tumour can now be measured with PET scans, the size of a tumour can be calculated in a three-dimensional way, and the amount of tumour DNA in the blood can be measured, Professor Hawkes said.
“This can inform next steps in patient care, so reliance on tumour bulk alone in prognosis and decision making is far less now in the modern era.”
