Functional Imaging for Response Assessment in ACC

Functional Imaging and Theranostics

Functional imaging for response assessment in adrenocortical carcinoma (ACC) refers to imaging approaches that attempt to characterize treatment effect through biologic activity, tissue composition, or tumor burden beyond simple changes in lesion diameter. Within ACC care, this topic sits under advanced-disease monitoring and treatment evaluation, most often in patients receiving systemic therapy for unresectable or metastatic disease.¹

Standard response assessment in ACC remains based on cross-sectional anatomic imaging, particularly CT and, in selected settings, MRI. Functional or functionally enriched methods have been explored because ACC lesions may undergo necrosis, attenuation change, or other internal alterations during treatment that are not fully captured by size-based criteria alone.¹ These methods include both tracer-based imaging and CT-derived alternative response frameworks, but the available ACC-specific literature is limited and methodologically heterogeneous.²¹

The evidence base is narrow and relies mainly on retrospective data and isolated case-level observations. As a result, functional imaging in ACC has not produced a validated response standard comparable to RECIST, and it cannot reliably replace conventional surveillance pathways.¹ The main supported conclusion is more modest: selected functional features may add interpretive or prognostic information in some patients, especially when anatomic imaging appears equivocal or shows limited size change despite ongoing therapy.¹

Diagnostic Context

Response assessment in ACC is usually performed with serial CT using standardized size-based criteria. This remains the most reproducible and broadly applicable approach across centers, particularly in metastatic disease and clinical trial settings.¹ Its main limitation is that biologically meaningful treatment effect may occur without immediate shrinkage, which can make stable-appearing disease difficult to interpret during active systemic therapy.¹

Functional assessment has been investigated to address that gap by estimating viable tumor activity or treatment-related internal change rather than relying solely on lesion diameter. What appears reasonably reliable is that these approaches may complement standard imaging in selected cases; what is not reliable is any claim that they provide a universally validated alternative response algorithm in ACC.¹

This distinction is important because the published ACC literature groups together modalities that are conceptually related but operationally different. Tracer uptake, attenuation change, and volumetric reduction may each reflect aspects of tumor biology, but they should not be treated as interchangeable markers of response.²¹

Functional Imaging Approaches

Tracer-based imaging

Tracer-based functional imaging has only sparse ACC-specific support for response assessment. The available literature shows that some ACCs may demonstrate gallium uptake in both primary and metastatic sites, supporting the biologic plausibility that activity-based imaging could contribute to follow-up in selected patients.²

However, this evidence is derived from case-level observation rather than cohort validation. It does not establish sensitivity, specificity, reproducibility, or thresholds for defining treatment response, so tracer avidity should be regarded as a possible tumor characteristic rather than a standardized biomarker for monitoring ACC.² In practical terms, tracer findings may occasionally provide supportive context, but they do not currently have a routine role comparable to CT-based assessment.

CT-based alternative response frameworks

The more clinically developed ACC literature concerns CT-based response criteria that extend beyond RECIST by incorporating attenuation or volumetric change. In metastatic ACC treated with EDP-mitotane, alternative frameworks such as Choi and volumetric criteria were feasible to apply and identified response patterns associated with better progression-free and overall survival.¹

This is the strongest signal in the available evidence because it links imaging-defined response to clinical outcomes rather than only describing appearance. Even so, the data remain retrospective, so prognostic association should not be interpreted as proof that these criteria are superior for all treatment decisions or should replace standard reporting.¹ The practical implication is narrower: attenuation- and volume-aware CT interpretation may help contextualize apparent stable disease and may support decisions about whether ongoing systemic therapy is still providing benefit.

Evidence and Clinical Implications

Across the included literature, the broad pattern is that non-size imaging features may carry clinically relevant information when conventional anatomic assessment is incomplete. The most persuasive evidence supports CT-based enriched response assessment in metastatic ACC receiving chemotherapy, where partial response by RECIST, Choi, or volumetric criteria correlated with more favorable outcomes.¹

By contrast, tracer-based evidence remains largely proof of principle. Demonstration of gallium avidity suggests that some ACCs are amenable to functional imaging, but it does not establish a validated framework for longitudinal response assessment or management change.² Clinically, this means CT-based alternative criteria currently offer more actionable support than tracer-based observations, although even CT-based approaches remain adjunctive rather than definitive.

Taken together, the literature suggests that functional imaging in ACC is most plausibly useful as a complementary interpretive and prognostic tool in advanced disease. What is relatively reliable is the possibility that biologically informed imaging may detect treatment effect not captured by size alone; what remains uncertain is how discordant functional and anatomic findings should alter management compared with established clinical and radiographic workflows.¹

Limitations and Pitfalls

The main limitations are evidentiary and conceptual. ACC is rare, and the published literature includes very few studies, with substantial variation in modality, clinical context, and endpoint definition.²¹ This limits generalizability and makes it difficult to compare techniques directly or define a standard sequence for their use.

A second pitfall is overinterpreting surrogate imaging signals. Changes in attenuation, volume, or tracer uptake may suggest altered tumor viability, but these measures remain indirect and may not translate cleanly into better treatment selection or longer survival on an individual-patient basis.¹ The practical implication is that functional findings should be interpreted alongside conventional imaging, symptoms, biochemical data when relevant, and overall treatment goals rather than in isolation.

Historical and case-based reports add biologic plausibility but have weak external validity. They are most useful for illustrating what may be possible in selected tumors, not for defining routine practice standards.²

Role in Management and Research

In current ACC management, functional imaging for response assessment remains subordinate to standard cross-sectional follow-up. CT or MRI continues to anchor surveillance, while functionally enriched interpretation may be considered in selected patients with heterogeneous metastatic disease, equivocal residual lesions, or apparently stable disease during systemic therapy.¹

From a research perspective, this remains an important area because ACC often shows complex treatment-related changes that size criteria alone may not fully capture. Retrospective data suggest that integrating attenuation or volumetric information into CT assessment may improve prognostic stratification, but prospective validation and standardization are still lacking.¹ Until stronger evidence emerges, functional imaging in ACC is best regarded as an adjunctive, hypothesis-generating component of response assessment rather than an established standalone standard.²¹

Included Articles

• PMID 10795713: This pediatric case report describes intense Ga-67 uptake in an infant adrenocortical carcinoma and suggests that, although Ga-67 scintigraphy is not essential for initial diagnosis, a baseline avidity study may support follow-up because primary and metastatic lesions can be Ga-67 positive.²

• PMID 32481732: In metastatic ACC treated with EDP-mitotane, CT response assessment using RECIST 1.1, Choi, and volumetric criteria was feasible, and partial response by any criterion correlated with better progression-free and overall survival. Concordant partial response across all three criteria identified a subgroup with especially favorable outcomes and may help guide whether to continue therapy.¹

References

Footnotes

1. Adrenocortical Carcinoma and CT Assessment of Therapy Response: The Value of Combining Multiple Criteria.. Cancers (Basel). 2020. PMID: 32481732. Local full text: 32481732.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹² ↩¹³ ↩¹⁴ ↩¹⁵ ↩¹⁶ ↩¹⁷ ↩¹⁸ ↩¹⁹

2. Evaluation of adrenocortical carcinoma in an infant using Ga-67 scintigraphy.. Clin Nucl Med. 2000. PMID: 10795713. Local full text: 10795713.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹