Cure Alveolar Soft Part Sarcoma International (iCureASPS)

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after the Initial Cycle of Neoadjuvant Chemotherapy in High-Grade Soft-Tissue Sarcomas


: 10.1158/1078-0432.CCR-08-2537 Published April 2009

Abstract

Purpose: In patients with soft-tissue sarcoma (STS), the early assessment of treatment responses is important. Using positron emission tomography/computed tomography (PET/CT) with [18F]fluorodeoxyglucose (FDG), we determined whether changes in tumor FDG uptake predict histopathologic treatment responses in high-grade STS after the initial cycle of neoadjuvant chemotherapy.

Experimental Design: From February 2006 to March 2008, 50 patients with resectable high-grade STS scheduled for neoadjuvant therapy and subsequent tumor resection were enrolled prospectively. FDG-PET/CT before (baseline), after the first cycle (early follow-up), and after completion of neoadjuvant therapy (late follow-up) was done. Tumor FDG uptake and changes were measured by standardized uptake values. Histopathologic examination of the resected specimen provided an assessment of treatment response. Patients with ≥95% pathologic necrosis were classified as treatment responders. FDG-PET/CT results were compared with histopathologic findings.

Results: At early follow-up, FDG uptake decreased significantly more in 8 (16%) responders than in the 42 (84%) nonresponders (−55% versus −23%; P = 0.002). All responders and 14 of 42 nonresponders had a ≥35% reduction in standardized uptake value between baseline and early follow-up. Using a ≥35% reduction in FDG uptake as early metabolic response threshold resulted in a sensitivity and specificity of FDG-PET for histopathologic response of 100% and 67%, respectively. Applying a higher threshold at late follow-up improved specificity but not sensitivity. CT had no value at response prediction.

Conclusion: A 35% reduction in tumor FDG uptake at early follow-up is a sensitive predictor of histopathologic tumor response. Early treatment decisions such as discontinuation of chemotherapy in nonresponding patients could be based on FDG-PET criteria.

Translational Relevance

In a previous study in Clinical Cancer Research, we reported that changes in glucose metabolic activity by [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) at the end of neoadjuvant treatment predicted histopathologic tumor responses in soft-tissue sarcomas (STS) with a high accuracy. However, imaging after completion of therapy has limited effect on patient management. Therefore, we investigated in the current study whether FDG-PET imaging after the initial cycle of neoadjuvant chemotherapy also provides accurate response predictions in high-grade STS patients. In this study, all nonresponders were identified by FDG-PET/computed tomography. Moreover, no treatment responders were missed by PET/computed tomography. This observation could now be translated to guiding therapeutic decisions in STS patients. The high negative predictive value of FDG-PET suggests that patients who do not achieve an early metabolic response should be switched to different therapeutic approaches or could be treated surgically earlier, which in turn could reduce toxicity associated with neoadjuvant treatments.

Optimal clinical evaluation of any cancer therapeutic hinges on our ability to monitor longitudinally treatment effects in patients. [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an established imaging technique that accurately predicts responses of diverse types of cancer to various treatments (1, 2). Disease-free survival (3), progression-free survival (4), overall survival (5), and degree of histopathologic necrosis in excised tissue (6–8) have been used as reference standards for validating FDG-PET findings and response predictions.

Glucose metabolic imaging has been used successfully in patients with esophageal cancer to determine whether neoadjuvant treatment should be continued or discontinued (9).

We have recently reported in soft-tissue sarcoma (STS) patients that changes in FDG tumor uptake from baseline to end of neoadjuvant treatment but not changes in tumor size by computed tomography (CT) identified accurately histopathologic responders (10).

Because neoadjuvant therapy is highly toxic (11, 12) and frequently ineffective (13), identifying histopathologic responders early during the course of therapy is of great importance. If this could be accomplished with FDG-PET imaging, successful treatments would be continued in responders but discontinued in nonresponding patients. The latter group of patients might then undergo surgery earlier or an alternative neoadjuvant therapy could be initiated.

The aim of the current prospective study was therefore to determine whether FDG-PET/CT after the initial cycle of neoadjuvant chemotherapy can identify those sarcoma patients who will be histopathologic responders (≥95% necrosis or fibrosis) following completion of neoadjuvant therapy. Further, we evaluated whether early changes in FDG uptake were as predictive for histopathologic responses as end of treatment FDG-PET evaluations.


https://clincancerres.aacrjournals.org/ ... /15/8/2856

CT Perfusion as an Imaging Biomarker in Monitoring Response to Neoadjuvant Bevacizumab and Radiation in Soft-Tissue Sarcomas: Comparison With Tumor Morphology, Circulating and Tumor Biomarkers, and Gene Expression


ol. 204: , Issue. 1, : Pages. W11-W18
(Issue publication date: January 2015)



OBJECTIVE. The purpose of this study was to evaluate the role of CT perfusion in monitoring response to neoadjuvant antiangiogenic and radiation therapy in resectable soft-tissue sarcomas and correlate the findings with tumor size, circulating and tumor biomarkers, and gene expression.

SUBJECTS AND METHODS. This phase II clinical trial included 20 patients (13 men and 7 women; mean age, 55 years) with soft-tissue sarcomas who were undergoing treatment with the antiangiogenic drug bevacizumab followed by bevacizumab, radiation, and surgical resection. The patients underwent CT perfusion and diagnostic contrast-enhanced CT at baseline, at 2 weeks after bevacizumab therapy, and after completion of bevacizumab and radiation therapy. Multiple CT perfusion parameters (blood flow, blood volume, mean transit time, and permeability) were correlated with tumor size, circulating and tumor biomarkers, and gene expression.

RESULTS. Two weeks after bevacizumab therapy, there was substantial fall in blood volume (31.9% reduction, p = 0.01) with more pronounced reduction in blood flow, blood volume, and permeability after treatment completion (53–64% reduction in blood flow, blood volume, and permeability; p = 0.001), whereas tumor size showed no significant change (p = 0.34). Tumors with higher baseline blood volume and lower baseline tumor size showed superior response to bevacizumab and radiation (p = 0.05). There was also an increase in median plasma vascular endothelial growth factor and placental-derived growth factor concentration after bevacizumab therapy paralleled by a decrease in tumor perfusion depicted by CT perfusion, although this was not statistically significant (p = 0.4). The baseline tumor microvessel density (MVD) correlated with blood flow (p = 0.04). At least 20 different genes were differentially expressed in tumors with higher and lower baseline perfusion.

CONCLUSION. CT perfusion is more sensitive than tumor size for monitoring early and late response to bevacizumab and radiation therapy. CT perfusion parameters correlate with MVD, and the gene expression levels of baseline tumors could potentially predict treatment response.



https://www.ajronline.org/doi/10.2214/AJR.13.12412

Article information

Eur Radiol Exp. 2020 Dec; 4: 2.
Published online 2020 Jan 3. doi: 10.1186/s41747-019-0134-1
PMCID: PMC6942076
PMID: 31900689


Abstract

A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2–10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria—so-called immune-related response criteria and then immune-related RECIST (irRECIST)—were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of “unconfirmed progression”, into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.

Keywords: Cell- and tissue-based therapy, Immunotherapy, Immune checkpoint inhibitors, Pseudoprogression, Response evaluation criteria in solid tumors (RECIST)
Key points

Immune checkpoint inhibitors remove inhibitory signals of T cell activation

Pseudoprogression occurs in 2–10% of patients treated with immunotherapy

An increase of tumour burden during immune checkpoint inhibitor treatment is more likely to reflect true progression than pseudo-progression

New criteria to assess immunotherapy are based on two major assumptions: new lesions do not preclude a progressive disease and a progression need to be confirmed on 4–8 weeks follow-up imaging

The knowledge of immune-related adverse events is of utmost importance and requires the exclusion of differentials, mainly of infectious or tumour nature



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942076/

We’ve come a long ways .
😊

“The advent of immunotherapy has led to durable responses for an increasing number of patients, including many who initially faced a poor prognosis. Unfortunately, those who respond to immunotherapy remain in the minority. Therefore, finding new ways to identify and stratify patients who are the most likely to respond to specific immunotherapeutic approaches is a major focus in the field.

Imaging a patient’s cancer—and the responses generated by the immune system—can provide key information that may guide immunotherapeutic treatment decisions throughout therapy. Advances in the imaging arena, such as the real-time, noninvasive visualization of specific cells, or the application of artificial intelligence (AI) to pathology, have garnered recent attention in the immunotherapy space.”



https://www.aacr.org/professionals/blog ... notherapy/