The beginning of the end for conventional RECIST — novel therapies require novel imaging approaches

Gerwing, Mirjam; Herrmann, Ken; Helfen, Anne; Schliemann, Christoph; Berdel, Wolfgang E.; Eisenblätter, Michel; Wildgruber, Moritz

doi:10.1038/s41571-019-0169-5

Cited by 102 publications

(72 citation statements)

References 178 publications

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“…In DCE-MRI, this was visible with morphological changes inside the lesion showing T2w hyperintense areas when compared with surrounding liver tissue (examples are shown in Figure 6 and Supplementary Figure S5), which is interpreted as hemorrhagic or necrotic areas. Since we have observed this phenomenon as a mechanism of action also in the mouse xenograft studies showing tumor swelling within the first days after treatment onset and intratumoral hemorrhage and necrosis in histological sections [14], this could lead to misinterpretation as early disease progression as is also described for immune checkpoint inhibitors [22]. Table 1 gives the patients in whom such an observation was made either in CEUS or in DCE-MRI.…”

Section: Dynamic Contrast-enhanced (Dce)-magnetic Resonance Imaging (mentioning

confidence: 79%

First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study

Schliemann

Gerwing

Heinzow

et al. 2020

Cancers

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Background: Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction. Methods: We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts. Results: MTD was 3 mg/m2 tTF-NGR/day × 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumoral hemorrhage and necrosis after tTF-NGR application. Pharmacokinetic analysis showed a t1/2(terminal) of 8 to 9 h without accumulation in daily administrations. Conclusion: tTF-NGR is safely applicable with this regimen. Imaging showed selective reduction of tumor blood flow and intratumoral hemorrhage and necrosis.

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Section: Dynamic Contrast-enhanced (Dce)-magnetic Resonance Imaging (mentioning

confidence: 79%

First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study

Schliemann

Gerwing

Heinzow

et al. 2020

Cancers

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“…For the treatment of lung cancer, early response evaluation provides guidance for appropriate individual therapy. In addition, survival depends on the biological behavior of the tumor rather than the residual tumor size after treatment (7,28). A residual tumor after treatment may contain inflammatory tissue, fibrotic tissue or resistant clones, and CT evaluation based on size is insufficient for these diseases.…”

Section: Discussionmentioning

confidence: 99%

A New Prognostic Index Combines the Metabolic Response and RECIST 1.1 to Evaluate the Therapeutic Response in Patients With Non-Small Cell Lung Cancer

et al. 2020

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Aim: Response Evaluation Criteria in Solid Tumors (RECIST) is occasionally insufficient for evaluation. We proposed a new prognostic index (NPI) that combines the standardized uptake value (SUV), metabolic tumor volume (MTV), and RECIST. Methods: In total, 116 patients with lung cancer who underwent consecutive positron emission tomography-computed tomography prior to and after the initial treatment were included. We formulated the NPI by estimating the hazard ratios of overall survival for MTV, SUV max , and D (tumor size based on RECIST). Progression-free survival (PFS) and overall survival (OS) were compared between RECIST and the NPI. Results: ROC curve analysis identified two cutoff values based on the NPI (≤−49.3% and ≥43.4%) to discriminate partial remission (NPR), stable disease (NSD) and progressive disease (NPD).

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“…Finally, technical issues in tumour response evaluation also arose with the use of immunotherapy [73]. Immune checkpoint inhibitors lead to new patterns of response [74,75]. Moreover, the goal of oncologic therapy has evolved from eradicating or curing to containing and controlling disease progression.…”

Section: So What?mentioning

confidence: 99%

ImmunoPET in Multiple Myeloma—What? So What? Now What?

Bailly

Chalopin

Gouard

et al. 2020

Cancers

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Despite constant progress over the past three decades, multiple myeloma (MM) is still an incurable disease, and the identification of new biomarkers to better select patients and adapt therapy is more relevant than ever. Recently, the introduction of therapeutic monoclonal antibodies (mAbs) (including direct-targeting mAbs and immune checkpoint inhibitors) appears to have changed the paradigm of MM management, emphasizing the opportunity to cure MM patients through an immunotherapeutic approach. In this context, immuno-positron emission tomography (immunoPET), combining the high sensitivity and resolution of a PET camera with the specificity of a radiolabelled mAb, holds the capability to cement this new treatment paradigm for MM patients. It has the potential to non-invasively monitor the distribution of therapeutic antibodies or directly monitor biomarkers on MM cells, and to allow direct observation of potential changes over time and in response to various therapeutic interventions. Tumor response could, in the future, be anticipated more effectively to provide individualized treatment plans tailored to patients according to their unique imaging signatures. This work explores the important role played by immunotherapeutics in the management of MM, and focuses on some of the challenges for this drug class and the significant interest of companion imaging agents such as immunoPET.

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The beginning of the end for conventional RECIST — novel therapies require novel imaging approaches

Cited by 102 publications

References 178 publications

First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study

First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study

A New Prognostic Index Combines the Metabolic Response and RECIST 1.1 to Evaluate the Therapeutic Response in Patients With Non-Small Cell Lung Cancer

ImmunoPET in Multiple Myeloma—What? So What? Now What?

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