Clinical judgment in the PET2 grey zone identifies patients who may avoid unnecessary treatment intensificationClinical judgment helps identify patients who can skip intensive lymphoma treatment

Frontiers in Medicine Published November 4, 2026 DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Note that clinical judgment in the PET2 grey zone may identify patients who achieve CMR on ABVD without intensification.

This retrospective study evaluates the impact of clinical judgment when interpreting PET2 results in patients with classical Hodgkin lymphoma. The study specifically examined the decision to either continue ABVD or intensify treatment (high-dose salvage plus autologous stem cell transplantation) for patients with a Deauville score of 4 or higher.

Patients who continued ABVD based on clinical judgment achieved a higher complete metabolic response rate at the first post-treatment PET (65% vs. 36%; p=0.036). Multivariable analysis showed that the decision to intensify was associated with higher lesion-to-liver delta SUV (OR 1.99) and lower age (OR 0.95). However, no statistically significant differences were found in 5-year overall survival (79.9% vs. 89.3%; p=0.106) or 10-year cumulative incidence of lymphoma-related death (12.7% vs. 7.1%; p=0.76).

The study is limited by its retrospective, single-center design. While the results suggest that clinical judgment in the 'grey zone' can identify patients who respond to ABVD and may not require intensive therapy, the study is not powered to determine if there is a difference in survival outcomes. The findings reflect real-world practice patterns rather than a definitive proof of superiority over automated thresholds.

How this fits prior evidence

This study addresses a gap in managing the 'grey zone' of PET2 results for classical Hodgkin lymphoma. While prior evidence notes that modern therapy yields >90% 5-year survival in early-stage patients, this study explores whether clinical judgment can identify patients who can safely avoid the toxicities of intensified treatment. It does not directly relate to the findings regarding benzene exposure or the use of novel agent-based regimens in older adults.

When a patient is diagnosed with Hodgkin lymphoma, doctors must decide how to treat them based on imaging. Sometimes, results fall into a "gray zone" where it is hard to tell if the current treatment is working or if the patient needs more intense, aggressive therapy. This study looked at how doctors handled that uncertainty in 51 patients who had a positive scan at a key midpoint.

Researchers found that when doctors used their clinical judgment to decide on treatment, many patients were able to stay on their current regimen instead of moving to more intense options. These patients showed a much higher rate of complete metabolic response—meaning their cancer showed no activity on scans—compared to those who were moved to intensified treatment. Specifically, 65% of those who stayed on their current path achieved a full response, while only 36% of those moved to intensified treatment did.

While the study was conducted at a single center and relied on past records, it suggests that careful clinical judgment can help identify who truly needs extra treatment. While the study did not show a statistically significant difference in survival rates between the two groups, it highlights how personalized decision-making can potentially spare patients from undergoing more aggressive procedures like stem cell transplants.

What this means for you:

Clinical judgment can help identify patients who can stay on standard treatment without increasing death risk.

Common questions

What is the benefit of using clinical judgment for treatment?

Clinical judgment helps doctors decide if a patient needs more intense treatment or can stay on their current plan. In this study, patients who stayed on their current treatment had a higher rate of complete metabolic response (65%) compared to those who were moved to intensified treatment (36%).

Does choosing a less intense treatment increase the risk of death?

The study did not find a significant difference in survival. The 10-year risk of lymphoma-related death was 12.7% for those who stayed on their current treatment and 7.1% for those who moved to intensified treatment, but this difference was not statistically significant.

How many patients were included in this study?

The study analyzed 51 patients who had a positive scan at the second PET scan (PET2) to help doctors decide between continuing their current treatment or moving to more intensive options.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedNov 2026

View Original Abstract ↓

BackgroundInterim PET after two cycles of ABVD (PET2) is a strong prognostic tool in Hodgkin lymphoma (HL), yet how clinicians use it to guide treatment in routine practice remains largely unexplored.MethodsWe retrospectively studied consecutive adults with classical HL treated 2010–2023 at one Italian centre. PET2 was assessed semiquantitatively: Deauville score (DS) 4 was assigned when the SUVmax of the hottest residual lesion exceeded the hepatic SUVmax reference. In PET2-positive patients (DS ≥ 4) the clinician decided whether to intensify (high-dose salvage ± autologous stem cell transplantation, ASCT) or continue. The primary endpoint was complete metabolic response (CMR, DS ≤ 3) at the first PET after PET2 (PETpost).ResultsOf 373 evaluable PET2, 53 (14%) were positive; 51 were analysed, treatment being modified in 28 (55%) and continued in 23 (45%). CMR at PETpost was more frequent in patients who continued ABVD (15/23, 65% vs. 10/28, 36%; p = 0.036). Residual metabolic activity at PET2 was lower in the continuation group (lesion-to-liver ΔSUV 0.9 vs. 3.5, p = 0.002). In exploratory multivariable analysis the decision to intensify was associated with lesion-to-liver ΔSUV (OR 1.99, p = 0.004) and younger age (OR 0.95, p = 0.033), and was much less frequent from 2015 onwards (OR 0.07, p = 0.009); in the model for CMR the decision was the only variable retained (OR 0.30, p = 0.039). After a median follow-up of 7.9 years, overall survival did not differ (5-year 79.9% vs. 89.3%, p = 0.106), nor the 10-year cumulative incidence of lymphoma-related death (12.7% vs. 7.1%, Gray's test p = 0.76), although patients continuing ABVD received a median of one treatment line and avoided ASCT in 87%.ConclusionIn a real-world setting without ultra-specialised PET review, clinicians resolved the grey zone of PET2 by weighting quantitative PET parameters alongside patient characteristics and evidence. This heuristic filter identified patients with borderline positivity responding to ABVD and spared them intensification without a detectable excess of lymphoma-related deaths, supporting the integration of semiquantitative PET parameters and clinical judgment into treatment decisions.

Clinical judgment in the PET2 grey zone identifies patients who may avoid unnecessary treatment intensificationClinical judgment helps identify patients who can skip intensive lymphoma treatment

How this fits prior evidence

Common questions

Study Details

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How this fits prior evidence

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