Immunotherapy response evaluation with 18F-FDG-PET in patients with advanced stage renal cell carcinoma

Abstract

BackgroundCT imaging is widely used for response evaluation of immunotherapy in patients with advanced stage renal cell carcinoma (RCC). However, this kind of treatment may not immediately be cytoreductive, although the treatment is successful. This poses new demands on imaging modalities. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) proved to be useful in monitoring the effect of several antitumour treatments. We investigated the potential of FDG-PET for the evaluation of response to immunotherapy.MethodsIn seven patients with metastasized RCC, who were treated with either interferon-alpha (IFN-α) monotherapy or a combination of IFN-α, interleukin-2 and 5-fluorouracil, FDG-PET was performed prior and after 5 and 9 weeks of treatment. Quantitative changes of glucose metabolic rate (MRGlu) were compared with changes in tumour size on CT imaging using Response Evaluation Criteria in Solid Tumors (RECIST) and to survival and progression-free survival.ResultsNo consistent changes in MRGlu were observed within different response groups. And no correlation with CT imaging, neither with survival or progression-free survival, was found.ConclusionIn contrast to the positive results reported on (chemo) therapy response evaluation with FDG-PET in different malignancies, this imaging modality appears not useful in response monitoring of immunotherapeutic modalities in RCC.

Future cancer research priorities in the USA: a Lancet Oncology Commission

“…294 One cannot simply use conventional Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 anatomical criteria to monitor immunotherapy because such therapy can have vastly different effects on the anatomic image of a tumour despite similar, often positive, patient out comes. 295,296 To address this difficulty, a consensus guideline known as iRECIST, a modified RECIST version 1·1 for immune-based therapeutics, has been developed for clinical trial protocols, but has not yet been validated to guide clinical practice. 297 18 F-FDG PET, a sensitive metabolic technique for detecting tumour progression, can also be somewhat misleading in guiding immunotherapy, even using the PERCIST criteria 298 because immune-cell influx causes a metabolic flare, suggesting a need for more specific molecular imaging agents.…”

Immunotherapy and the role of imaging

“…Those authors developed criteria comprised of anatomic and functional information that predicted eventual response with 100% sensitivity, 93% specificity, and 95% accuracy. FDG‐PET/CT has demonstrated benefit in evaluating the response of patients with melanoma to treatment with BRAF and MEK inhibitors but has proven to be inadequate in examining responses to immunotherapy for other cancers, such as renal cell carcinoma …”

“…FDG-PET/CT has demonstrated benefit in evaluating the response of patients with melanoma to treatment with BRAF and MEK inhibitors 18 but has proven to be inadequate in examining responses to immunotherapy for other cancers, such as renal cell carcinoma. 19…”

The relevance of positron emission tomography response in non-small cell lung cancer

“…The ability of FDG-PET to characterize response to immunotherapy has been investigated in a small series of patients with renal cell cancer (RCC). In 7 RCC patients treated with interferon-alpha (IFN-α) monotherapy or a combined IFN-, interleukin-2 and 5-Xuorouracil FDG-PET was not found to correlate with responses seen in CT imaging or with clinical outcomes [81]. Much research is still needed to evaluate implications of immune therapies for PET-based monitoring strategies [74]; however, PET approaches may prove to be central to response assessments of these new, innovative and promising therapies for patients with NSCLC.…”