Therapy Response Assessment Research Articles

Diagnosis and treatment of lung cancer using nuclear medicine techniques - current state of the art.

Lung cancer is the leading cause of cancer-related death worldwide. Planar radiography and computed tomography are the most common imaging modalities used in diagnosis, staging, and therapy response assessment. However, the role of nuclear methods in assessing the severity of the disease and the effectiveness of treatment has increased in recent years. Introducing these diagnostic modalities into standard practice in lung cancer may contribute to the personalization of treatment. In this review, we summarize the current knowledge of nuclear medicine techniques in the diagnosis and treatment of lung cancer.

18F-FDG PET/CT in therapy response assessment: oligometastatic colorectal cancer

BackgroundColorectal cancer (CRC) is one of the most widespread cancers worldwide, leading to roughly half a million deaths yearly. The European Society for Medical Oncology defined oligometastatic CRC as a disease with few metastases affecting a small number of sites (5 or occasionally more metastases involving up to 3 sites). In addition to colonoscopy, magnetic resonance imaging (MRI), and digital rectal examination in patients with rectal cancer, response monitoring of CRC is commonly carried out by CT imaging. The use of PET for response monitoring has not been adapted into colorectal cancer guidelines until 2021. However, 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18F-FDG PET/CT) offers a higher efficiency for assessing treatment outcomes than traditional imaging. This study aims to explore the utility of 18F-FDG PET/CT imaging in the assessment of therapy response in patients with oligometastatic colorectal cancer (OMCRC).ResultsThe study comprised 79 OMCRC patients (35 and 44 patients with synchronous and metachronous metastasis respectively). In synchronous disease patients 18F-FDG PET/CT scan showed significant reduction of mean size and standardized uptake value (SUV) of the primary site lesions and the mean SUV of lymph nodes (LNs) and lung metastases (P = 0.00, 0.00,0.00, and 0.002, respectively) while, metachronous disease patients had significant reduction in the mean size and SUV of LNs (1.8 ± 0.7 & 4.7 ± 1.3 versus 1.1 ± 1.0 & 2.9 ± 3.0, P = 0.001 & 0.00 respectively) and the mean SUV of peritoneal metastases (8.7 ± 4.7 versus 6.8 ± 2.4 P = 0.00). Partial metabolic response (PMR) and stable metabolic disease (SMD) were found in more than half of the patients (58.2%). Complete metabolic response (CMR) and Progressive metabolic disease (PMD), on the other hand, were achieved in 41.8% of patients [17 (21.5%) and 16 (20.3%) patients, respectively] with substantially higher CMR rate in metachronous disease than synchronous disease [14.0 (31.8%) versus 3.0 (8.5%) patients, P = 0.015)].Conclusions18F-FDG PET/CT can be added as a valuable imaging method for identifying responders and non-responders among OMCRC patients, as it optimizes the selection of patients with CRC for local therapy and has a significant impact on directing their therapy course. Oligometastatic colorectal cancer seems to be a controllable disease with hopeful therapy outcomes, particularly for those with metachronous metastases.

Comparative Evaluation of 99mTc-Octreotide for Diagnostic Accuracy Assessment and Localization of 177Lu-DOTA-TATE in Neuroendocrine Tumors.

Neuroendocrine tumors, due to uncommon and multi-centric origin, pose a clinical challenge for their diagnosis and treatment. Developing countries where Ga-68 DOTA-TOC/NOC PET imaging is very limited and costly, 99mTc based SSR imaging can be used as the key tool for its diagnosis and assessment of therapy response. Hence we used two different 99mTc-radiopharmaceuticals for NET imaging designated as RP-1 and RP-2 for clinical assessment and peptide receptor therapy response of 177Lu-DOTA-TATE by manually synthesized acetate buffer. 99mTc- labeled RP-1 and RP-2 sensitivity, specificity; positive and negative predictive values were calculated and compared by SPECT/CT images for utilization in peptide receptor radionuclide therapy (PRRT). Sodium-pertechnetate was used for labeling both radiopharmaceuticals, while 177Lu nca (0.04 N HCl) DOTA-TATE was synthesized by 0.1M ammonium acetate/ascorbic acid. 75 patients of known primary NET imaging with RP-1 and RP-2 were evaluated for SRR avidity and 3 were selected for PRRT. All images were correlated with 68Ga-DOTA-TOC scan, histopathology, CT and/or MRI reports. Out of 75 patients, the somatostatin receptor imaging of 39 patients of neuro-endocrine was performed with RP-1, found 23 as true positive, 7 as true negative with sensitivity, specificity, PPV and NPV of 71.87%, 100%, 100% and 43.75%, whereas 36 images with RP-2 calculated 22 T/P, 6 as T/N, 8 as F/N, with 75.8%, 100%, 100% and 50% respectively. Their 177Lu-DOTA-TATE SPECT/CT revealed specific localization of therapeutic radionuclide. 99mTc-imaging of RP-2, as compared to RP-1, had better efficiency and sensitivity and could effectively be used as an alternative to Ga-68 DOTA/TOC PET imaging and Lu-177 DOTA-TATE PRRT therapy response evaluation.

Assessment of Response to Neoadjuvant Systemic Treatment in Triple-Negative Breast Cancer Using Functional Tumor Volumes from Longitudinal Dynamic Contrast-Enhanced MRI

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement (PE) and signal enhancement ratio (SER) thresholds. The Mann-Whitney test was used to compare the performance of the FTVs at C2 and C4. Of the 100 patients, 49 (49%) had a pathologic complete response (pCR) and 51 (51%) had a non-pCR. The maximum area under the receiving operating characteristic curve (AUC) for predicting the treatment response was 0.84 (p < 0.001) for FTV at C4 followed by FTV at C2 (AUC = 0.82, p < 0.001). The FTV measured at baseline was not able to discriminate pCR from non-pCR. FTVs measured on DCE MRI at C2, as well as at C4, of NAST can potentially predict pCR and non-pCR in TNBC patients.

Patient-derived organoids as a promising preclinical model for assessing therapy response in bladder cancer

Patient-derived organoids as a promising preclinical model for assessing therapy response in bladder cancer

Role of artificial intelligence in risk prediction, prognostication, and therapy response assessment in colorectal cancer: current state and future directions.

Artificial Intelligence (AI) is a branch of computer science that utilizes optimization, probabilistic and statistical approaches to analyze and make predictions based on a vast amount of data. In recent years, AI has revolutionized the field of oncology and spearheaded novel approaches in the management of various cancers, including colorectal cancer (CRC). Notably, the applications of AI to diagnose, prognosticate, and predict response to therapy in CRC, is gaining traction and proving to be promising. There have also been several advancements in AI technologies to help predict metastases in CRC and in Computer-Aided Detection (CAD) Systems to improve miss rates for colorectal neoplasia. This article provides a comprehensive review of the role of AI in predicting risk, prognosis, and response to therapies among patients with CRC.

Can triphasic hepatic multislice CT validate the LI-RADS treatment response algorithm after trans-catheter arterial chemoembolization treatment of hepatocellular carcinoma?

BackgroundOur aim is to evaluate LI-RADS-TR algorithm and its ability to assess the viability of TACE-treated HCC. We prospectively evaluated 100 patients with known HCC, treated with TACE and came for follow-up to assess therapy response and to plan the next step in treatment using triphasic CT study. Imaging response was evaluated according to LI-RADS-TR algorithm and compared to modified Response Evaluation Criteria in Solid Tumors (mRECIST) arterial phase hyperenhancement (APHE) criterion. Reference standard for “viable” tumors in treated observations included presence of strong tumor hyperenhancement in arterial phase and washout in the delayed phase which also shows dense accumulation of iodized oil in the target lesion.ResultsWhen equivocal observations were considered as LR-TR viable, LR-TR viable resulted in 92.31% sensitivity, 83.33% specificity and 88% accuracy. On the other side when equivocal observations were considered as LR-TR nonviable, it resulted in 84.62% while the specificity increased to 100% with increased accuracy (92%). The mRECIST criteria for viable tumors (presence of APHE) showed sensitivity of 84.62% and specificity of 75%. mRECIST and LR-TR sensitivities were the same when equivocal lesions were considered as nonviable and lower mRECIST than LR-TR when equivocal lesions were considered as viable, while specificities were higher in LR-TR viable being 100% when equivocal lesions were considered as nonviable, 83.33% when equivocal lesions were considered as viable and 75% in mRECIST-viable.ConclusionsLR-TR algorithm showed good diagnostic performance compared to mRECIST, with high specificity and sensitivity when equivocal lesions were considered as nonviable, as well as improved accuracy.

An integrated investigation of structural and pathway alteration caused by PIK3CA and TP53 mutations identified in cfDNA of metastatic breast cancer.

In peripheral blood, cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which indicates molecular abnormalities in metastatic breast tumor tissue. The sequencing of cfDNA of Metastatic Breast Cancer (MBC) patients allows assessment of therapy response and noninvasive treatment. In the proposed study, clinically significant alterations in PIK3CA and TP53 genes associated with MBC resulting in a missense substitution of His1047Arg and Arg282Trp from an next-generation sequencing-based multi-gene panel were reported in a cfDNA of a patient with MBC. To investigate the impact of the reported mutation, we used molecular docking, molecular dynamics simulation, network analysis, and pathway analysis. Molecular Docking analysis determined the distinct binding pattern revealing H1047R-ATP complex has a higher number of Hydrogen bonds (H-bonds) and binding affinity with a slight difference compared to the PIK3CA-ATP complex. Following, molecular dynamics simulation for 200 ns, of which H1047R-ATP complex resulted in the instability of PIK3CA. Similarly, for TP53 mutant R282W, the zinc-free state (apo) and zinc-bounded (holo) complexes were investigated for conformational change between apo and holo complexes, of which the holo complex mutant R282W was unstable. To validate the conformational change of PIK3CA and TP53, 80% mutation of H1047R in the kinase domain of p110α expressed ubiquitously in PIK3CA protein that alters PI3K pathway, while R282W mutation in DNA binding helix (H2) region of P53 protein inhibits the transcription factor in P53 pathway causing MBC. According to our findings, the extrinsic (hypoxia, oxidative stress, and acidosis); intrinsic factors (MYC amplification) in PIK3CA and TP53 mutations will provide potential insights for developing novel therapeutic methods for MBC therapy.

Progesterone Receptor-Mediated Regulation of Cellular Glucose and 18F-Fluorodeoxyglucose Uptake in Breast Cancer.

Positron emission tomography imaging with 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) is used clinically for initial staging, restaging, and assessing therapy response in breast cancer. Tumor FDG uptake in steroid hormone receptor-positive breast cancer and physiologic FDG uptake in normal breast tissue can be affected by hormonal factors such as menstrual cycle phase, menopausal status, and hormone replacement therapy. The purpose of this study was to determine the role of the progesterone receptor (PR) in regulating glucose and FDG uptake in breast cancer cells. PR-positive T47D breast cancer cells treated with PR agonists had increased FDG uptake compared with ethanol control. There was no significant change in FDG uptake in response to PR agonists in PR-negative MDA-MB-231 cells, MDA-MB-468 cells, or T47D PR knockout cells. Treatment of T47D cells with PR antagonists inhibited the effect of R5020 on FDG uptake. Using T47D cell lines that only express either the PR-A or the PR-B isoform, PR agonists increased FDG uptake in both cell types. Experiments using actinomycin D and cycloheximide demonstrated the requirement for both transcription and translation in PR regulation of FDG uptake. GLUT1 and PFKFB3 mRNA expression and the enzymatic activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were increased after progestin treatment of T47D cells. Thus, progesterone and progestins increase FDG uptake in T47D breast cancer cells through the classical action of PR as a ligand-activated transcription factor. Ligand-activated PR ultimately increases expression and activity of proteins involved in glucose uptake, glycolysis, and the pentose phosphate pathway.

Assessment and prediction of glioblastoma therapy response: challenges and opportunities.

Glioblastoma is the most aggressive type of primary adult brain tumour. The median survival of patients with glioblastoma remains approximately 15 months, and the 5-year survival rate is <10%. Current treatment options are limited, and the standard of care has remained relatively constant since 2011. Over the last decade, a range of different treatment regimens have been investigated with very limited success. Tumour recurrence is almost inevitable with the current treatment strategies, as glioblastoma tumours are highly heterogeneous and invasive. Additionally, another challenging issue facing patients with glioblastoma is how to distinguish between tumour progression and treatment effects, especially when relying on routine diagnostic imaging techniques in the clinic. The specificity of routine imaging for identifying tumour progression early or in a timely manner is poor due to the appearance similarity of post-treatment effects. Here, we concisely describe the current status and challenges in the assessment and early prediction of therapy response and the early detection of tumour progression or recurrence. We also summarize and discuss studies of advanced approaches such as quantitative imaging, liquid biomarker discovery and machine intelligence that hold exceptional potential to aid in the therapy monitoring of this malignancy and early prediction of therapy response, which may decisively transform the conventional detection methods in the era of precision medicine.

Meta-Analysis of the Test-Retest Repeatability of [18F]-Fluorodeoxyglucose Standardized Uptake Values: Implications for Assessment of Tumor Response.

Currently, guidelines for PET with 18F-fluorodeoxyglucose (FDG-PET) interpretation for assessment of therapy response in oncology primarily involve visual evaluation of FDG-PET/CT scans. However, quantitative measurements of the metabolic activity in tumors may be even more useful in evaluating response to treatment. Guidelines based on such measurements, including the European Organization for Research and Treatment of Cancer Criteria and PET Response Criteria in Solid Tumors, have been proposed. However, more rigorous analysis of response criteria based on FDG-PET measurements is needed to adopt regular use in practice. Well-defined boundaries of repeatability and reproducibility of quantitative measurements to discriminate noise from true signal changes are a needed initial step. An extension of the meta-analysis from de Langen and colleagues (2012) of the test-retest repeatability of quantitative FDG-PET measurements, including mean, maximum, and peak standardized uptake values (SUVmax, SUVmean, and SUVpeak, respectively), was performed. Data from 11 studies in the literature were used to estimate the relationship between the variance in test-retest measurements with uptake level and various study-level, patient-level, and lesion-level characteristics. Test-retest repeatability of percentage fluctuations for all three types of SUV measurement (max, mean, and peak) improved with higher FDG uptake levels. Repeatability in all three SUV measurements varied for different lesion locations. Worse repeatability in SUVmean was also associated with higher tumor volumes. On the basis of these results, recommendations regarding SUV measurements for assessing minimal detectable changes based on repeatability and reproducibility are proposed. These should be applied to differentiate between response categories for a future set of FDG-PET-based criteria that assess clinically significant changes in tumor response.

Currently available molecular analyses for personalized tumor therapy (Review).

Targeted therapies are becoming more common and genetic tumor profiling is becoming more precise and affordable. The aim of the present review was to demonstrate the importance of molecular analyses in tumors, summarize the current situation, provide an outlook on how to improve diagnosis to facilitate individualized therapy, including the use of specific methodologies for tumor marker analysis to improve patient treatment. Most predicted metabolomic and proteomic biomarkers have not progressed from the laboratory to clinical trials, as most of the trials were stopped at the initial stage of biomarker identification. The use of liquid biopsies as a clinical tool improves cancer screening, diagnosis and prognosis; furthermore, is able to improve the classification of more diverse disease entities, assess therapy response and identify treatment-resistant clones, allowing for more stringent patient monitoring. Based on specific clinical populations and the unique molecular features of a cancer, the identification of a suitable targeted therapy may be accomplished. The present review provides insight into cancer genomic testing in the clinical setting and the available methods, supporting the prioritization of molecular therapeutic tumor targeting.

ABCL-007 Semiquantitative Measurements of Standard-Uptake-Value (ΔSUV) in Assessment of Patients Response and Outcomes in Aggressive Lymphomas

Positron emission tomography (PET) with 18-fluoro-2-deoxy-D-glucose ([18 F] FDG) is an essential tool for accurate staging, early, and late therapy response assessment in all FDG-avid lymphomas. To evaluate the accuracy of ΔSUV max in assessment of response to treatment in patients with lymphoma. This study was conducted between October 2019 and October 2021. Seventy-three patients diagnosed as high-grade lymphoma or Hodgkin disease (HD) were enrolled in the study. PET/CT examinations were performed at baseline (PET0), after the second, the fourth cycle of chemotherapy and at the end of treatment. PET-CT scans were analyzed according to the Deauville 5-point scale (5-PS). According to SUV-based assessment, PET/CT was considered negative when ΔSUV max at 2nd cycle (PET0-2) is more than 66% and ΔSUV max at 4th cycle (PET0-4) is more than 70%, respectively. The change in activity (ΔSUV) from initial (SUVmax1) to later scans (SUVmax2) was calculated as: SUV (%) = 100 x ([SUVmax2/SUVmax1] -1). Biopsy was taken if PET 2 or 4 is visually positive with negative delta SUV max, or in case of new lesions if other sites have improved. SUV uptake values at baseline were 16.30 ± 9.36 in NHL versus 12.55 ± 6.78 in HL. After 2 cycles of chemotherapy, (78.1%) had negative PET based on ΔSUV max raised to (86.3%) by the end of 4th cycle and this was different from 5PS where only (60.5%) raised to (74.4%) after the 4th cycle. In comparison with results of biopsy, ΔSUV0-2 has sensitivity 80%, specificity 94.1%, accuracy 90.91 % with P value (0.001) also, ΔSUV0-4 has sensitivity 80%, specificity 100%, accuracy 95.45 % with high agreement with P value (<0.001). On the contrary, the visual 5-PS analysis 0-2 specificity 17.65%, accuracy 36.36 with P value (<0.321). Also, the visual 5-PS analysis 0-4 specificity 41.18 %, accuracy 54.55% with P value (<0.082). After 4 cycles 22 patients needed to undergo biopsy because inconclusive results of PET. Comparison reveled that using ΔSUV max demonstrated higher specificity. ΔSUV max is comparable to biopsy and significantly more accurate than Deauville criteria in assessment of response to treatment.

Peritoneal regression grading score (PRGS) in peritoneal metastasis: how many biopsies should be examined?

The four-tied peritoneal regression grading score (PRGS) is increasingly used to evaluate the response ofperitoneal metastases (PM) to chemotherapy. The minimal number of peritoneal biopsies needed for PRGS determination remains unclear. A prospective cohort of 89 PM patients treated with 210 pressurized intraperitoneal aerosol chemotherapy (PIPAC) cycles was investigated. Four biopsies from every abdominal quadrant were recommended. Histological tumor response was defined as a stable or decreasing mean PRGS between therapy cycles, progression increasing. We compared the diagnostic uncertainty induced by missing biopsies to the histological response. A total of 49 patients had at least two PIPAC and were eligible for therapy response assessment. Mean PRGS decreased from 2.04 (CI 5-95% 1.85-2.27) to 1.79 (CI 5-95% 1.59-2.01), p=0.14, as a proof of therapy effectiveness. 35(71.4%) patients had a stable or decreasing PRGS (therapy response), 14 (28.6%) a PRGS increase (disease progression). Histology showed agreement between four biopsies in 42/210 laparoscopies (20%), between≥3 biopsies in 103 (49%), and between≥2 biopsies in 169 laparoscopies (81%). Mean loss of information with one missing biopsy was 0.11 (95% CI=0.13) PRGS points, with two missing biopsies 0.18 (95% CI 0.21). In 9/49 patients (18.3%), the loss of information with one less biopsy exceeded the change in PRGS under therapy. A minimum of three biopsies is needed todiagnose PM progression with an accuracy superior to 80%. Missing biopsies often result in a false diagnosis of tumor progression.

Contrast-Enhanced Mammography Versus MRI in the Evaluation of Neoadjuvant Therapy Response in Patients With Breast Cancer: A Prospective Study.

BACKGROUND. Contrast-enhanced mammography (CEM) is rapidly expanding as a credible alternative to MRI in various clinical settings. OBJECTIVE. The purpose of this study was to compare CEM and MRI for neoadjuvant therapy (NAT) response assessment in patients with breast cancer. METHODS. This prospective study included 51 patients (mean age, 46 ± 11 [SD] years) with biopsy-proven breast cancer who were candidates for NAT from May 2015 to April 2018. Patients underwent both CEM and MRI before, during, and after NAT (pre-NAT, mid-NAT, and post-NAT, respectively). Post-NAT CEM included a 6-minute delayed acquisition. One breast radiologist with experience in CEM reviewed CEM examinations; one breast radiologist with experience in MRI reviewed MRI examinations. The radiologists assessed for the presence of an enhancing lesion; if an enhancing lesion was detected, its size was measured. RECIST version 1.1 response assessment categories were derived. Pathologic complete response (pCR) was defined as absence of both invasive cancer and ductal carcinoma in situ (DCIS). RESULTS. Of 51 patients, 16 achieved pCR. CEM yielded systematically lower size measurements compared with MRI (mean difference, -0.2 mm for pre-NAT, -0.7 mm for mid-NAT, and -0.3 mm for post-NAT). All post-NAT imaging tests yielded systematically larger size measurements compared with pathology (mean difference, 0.8 mm for CEM, 1.2 mm for MRI, and 1.9 mm for delayed CEM). Of 12 patients with residual DCIS, an enhancing lesion was detected in seven on post-NAT CEM, eight on post-NAT MRI, and nine on post-NAT delayed CEM. Agreement of RECIST response categories between CEM and MRI, expressed as kappa coefficient, was 0.791 at mid-NAT and 0.871 at post-NAT. For detecting pCR by post-NAT imaging, sensitivity and specificity were 81% and 83% for CEM, 100% and 86% for MRI, and 81% and 89% for delayed CEM. Sensitivity was significantly higher for MRI than CEM (p = .001) and delayed CEM (p = .002); remaining comparisons were not significant (p > .05). CONCLUSION. After NAT for breast cancer, CEM and MRI yielded comparable assessments of lesion size (both slightly overestimated vs pathology) and RECIST categories and showed no significant difference in specificity for pCR. MRI had higher sensitivity for pCR. Delayed CEM acquisition may help detect residual DCIS. CLINICAL IMPACT. Although MRI remains the preferred test for NAT response monitoring, the findings support CEM as a useful alternative when MRI is contraindicated or not tolerated.

The role of PET/CT in large vessel vasculitis and related disorders: diagnosis, extent evaluation and assessment of therapy response

Large vessel vasculitides (LVV) are defined as chronic inflammatory disorders that affect the arteries with two major variants being distinguished: giant cell arteritis (GCA) and Takayasu's arteritis (TAK). These often present with nonspecific constitutional symptoms which makes an accurate diagnosis often challenging. Nevertheless, timely diagnosis is of utmost importance to initiate treatment and to avoid potential life-threatening complications. [18F]FDG-PET/CT is nowadays widely accepted as useful tool to aid in the diagnosis of large vessel vasculitis. However, its role to monitor disease activity and to predict disease relapse during follow-up is less obvious since vascular [18F]FDG uptake can be detected in the absence of clinical or biochemical signs of disease activity. In addition to the two major variants, [18F]FDG-PET/CT has shown promise in (peri-)aortitis and related disorders. This article aims to provide an update on the current knowledge and limitations of [18F]FDG-PET/CT for the diagnosis and assessment of treatment response in LVV. Furthermore, other radiopharmaceuticals targeting key components of the vascular immune system are being discussed which could provide an interesting alternative to image vascular inflammation in LVV.

Prospective of 31 P MR Spectroscopy in Hepatopancreatobiliary Cancer: A Systematic Review of the Literature.

The incidence of liver and pancreatic cancer is rising. Patients benefit from current treatments, but there are limitations in the evaluation of (early) response to treatment. Tumor metabolic alterations can be measured noninvasively with phosphorus (31 P) magnetic resonance spectroscopy (MRS). To conduct a quantitative analysis of the available literature on 31 P MRS performed in hepatopancreatobiliary cancer and to provide insight into its current and potential for therapy (non-) response assessment. Patients with hepatopancreatobiliary cancer. FIELD STRENGTH/SEQUENCE: 31 P MRS. The PubMed, EMBASE, and Cochrane library databases were systematically searched for studies published to 17 March 17, 2022. All 31 P MRS studies in hepatopancreatobiliary cancer reporting 31 P metabolite levels were included. Relative differences in 31 P metabolite levels/ratios between patients before therapy and healthy controls, and the relative changes in 31 P metabolite levels/ratios in patients before and after therapy were determined. The search yielded 10 studies, comprising 301 subjects, of whom 132 (44%) healthy volunteers and 169 (56%) patients with liver cancer of various etiology. To date, 31 P MRS has not been applied in pancreatic cancer. In liver cancer, alterations in levels of 31 P metabolites involved in cell proliferation (phosphomonoesters [PMEs] and phosphodiesters [PDEs]) and energy metabolism (ATP and inorganic phosphate [Pi]) were observed. In particular, liver tumors were associated with elevations of PME/PDE and PME/Pi compared to healthy liver tissue, although there was a broad variety among studies (elevations of 2%-267% and 21%-233%, respectively). Changes in PME/PDE in liver tumors upon therapy were substantial, yet very heterogeneous and both decreases and increases were observed, whereas PME/Pi was consistently decreased after therapy in all studies (-13% to -76%). 31 P MRS has great potential for treatment monitoring in oncology. Future studies are needed to correlate the changes in 31 P metabolite levels in hepatopancreatobiliary tumors with treatment response. 3 TECHNICAL EFFICACY: Stage 2.

A narrative review on current imaging applications of artificial intelligence and radiomics in oncology: focus on the three most common cancers.

The use of artificial intelligence (AI) and radiomics in the healthcare setting to advance disease diagnosis and management and facilitate the creation of new therapeutics is gaining popularity. Given the vast amount of data collected during cancer therapy, there is significant concern in leveraging the algorithms and technologies available with the underlying goal of improving oncologic care. Radiologists will attain better precision and effectiveness with the advent of AI technology, making machine-assisted medical services a valuable and important option for future oncologic medical care. As a result, it is critical to figure out which specific radiology activities are best positioned to gain from AI and radiomics models and methods of oncologic imaging, while also considering the algorithms' capabilities and constraints. Our purpose is to overview the current evidence and future prospects of AI and radiomics algorithms used in oncologic imaging efforts with an emphasis on the three most frequent cancers worldwide, i.e., lung cancer, breast cancer and colorectal cancer. We discuss how AI and radiomics could be used to detect and characterize cancers and assess therapy response.

P885: PROSPECTIVE ASSESSMENT OF MYELOMA TUMOUR BURDEN AND BONE DISEASE USING DW-MRI AND EXPLORATORY BONE BIOMARKERS

Background: Key clinical priorities for multiple myeloma (MM) are to reduce tumour burden and complications, of which lytic bone disease is the major cause of morbidity. To guide treatment, there is a pressing need for biomarkers that can accurately quantify MM tumour burden and associated bone disease. To this end, Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) and bone turnover markers are promising radiological and serum metrics, respectively, although their clinical value in prospective assessment is unclear. Aims: LOOMIS was a single-centre observational cohort study that evaluated the relative merits of DW-MRI and bone turnover markers in prospectively assessing tumour burden and bone disease when added to standard clinical assessment, in patients with MM and monoclonal gammopathy of undetermined significance (MGUS). Methods: A total of 67 patients were enrolled (14 newly diagnosed MM, 12 relapsed MM, 15 smouldering MM, 14 MGUS and 12 healthy volunteers) between March 2018 and March 2020. At baseline (and 6-month follow-up for MM/MGUS), participants had a DW-MRI scan and serum measurements of established (P1NP, CTX-1, ALP) and exploratory (DKK1, sclerostin, RANKL:OPG ratio) bone turnover markers. MM/MGUS patients additionally had standard myeloma bloods and Dual-Energy X-ray Absorptiometry (DXA) at each visit, as correlates of tumour burden and bone loss. DW-MRI scans were double reported by expert Radiologists for Apparent Diffusion Coefficient (ADC) measurements of lytic bone lesion(s), and Myeloma Response Assessment and Diagnosis System (MY-RADS) Response Assessment Category (RAC) scoring. Patients were classified by International Myeloma Working Group (IMWG) response criteria as a clinical correlate of therapy response. Results: On assessment of baseline tumour burden, there was no correlation between single lesion DW-MRI ADC and serum paraprotein [p>0.05]; however, there was moderate positive correlation between serum DKK1 and serum paraprotein [r=0.39, p=0.04]. At follow-up, radiological MY-RADS RAC scoring correlated with conventional IMWG response criteria [p=0.015]; additionally, longitudinal relative change in serum DKK1 differed between IMWG-defined therapy responders (37% decrease) and non-responders (15% increase) [p<0.01]. On baseline assessment of bone loss, there was moderate positive correlation between serum sclerostin and DXA bone mineral density at femoral neck [r=0.40, p<0.01] and lumbar spine [r=0.54, p<0.001]. At follow-up, there was a moderate negative correlation between longitudinal % change in the RANKL:OPG ratio and % change in DXA bone mineral density at femoral neck [r= -0.45, p<0.01]. Summary/Conclusion: Our prospective trial validates DW-MRI-based MY-RADS RAC scoring as a qualitative radiological tool to assess therapy response. Whilst previous work has supported single lytic lesion ADC measurements as a correlate of tumour volume, we did not find this; small sample size and prior chemotherapy in our study may have limited our ability to detect this. In comparison, serum bone turnover markers such as DKK1 may provide a more global measure to quantify myeloma burden both at baseline diagnosis and longitudinally with therapy. Additionally, our data highlight serum sclerostin and RANKL:OPG ratio as potential biomarkers to assess and monitor bone loss. Overall, our study highlights emerging radiological and serum biomarkers of tumour burden and associated bone loss in MM and MGUS, which merit further exploration alongside uniformly treated cohorts, to better understand their clinical utility.

Combining Deep Learning and Radiomics for Automated, Objective, Comprehensive Bone Marrow Characterization From Whole-Body MRI: A Multicentric Feasibility Study.

Disseminated bone marrow (BM) involvement is frequent in multiple myeloma (MM). Whole-body magnetic resonance imaging (wb-MRI) enables to evaluate the whole BM. Reading of such whole-body scans is time-consuming, and yet radiologists can transfer only a small fraction of the information of the imaging data set to the report. This limits the influence that imaging can have on clinical decision-making and in research toward precision oncology. The objective of this feasibility study was to implement a concept for automatic, comprehensive characterization of the BM from wb-MRI, by automatic BM segmentation and subsequent radiomics analysis of 30 different BM spaces (BMS). This retrospective multicentric pilot study used a total of 106 wb-MRI from 102 patients with (smoldering) MM from 8 centers. Fifty wb-MRI from center 1 were used for training of segmentation algorithms (nnU-Nets) and radiomics algorithms. Fifty-six wb-MRI from 8 centers, acquired with a variety of different MRI scanners and protocols, were used for independent testing. Manual segmentations of 2700 BMS from 90 wb-MRI were performed for training and testing of the segmentation algorithms. For each BMS, 296 radiomics features were calculated individually. Dice score was used to assess similarity between automatic segmentations and manual reference segmentations. The "multilabel nnU-Net" segmentation algorithm, which performs segmentation of 30 BMS and labels them individually, reached mean dice scores of 0.88 ± 0.06/0.87 ± 0.06/0.83 ± 0.11 in independent test sets from center 1/center 2/center 3-8 (interrater variability between radiologists, 0.88 ± 0.01). The subset from the multicenter, multivendor test set (center 3-8) that was of high imaging quality was segmented with high precision (mean dice score, 0.87), comparable to the internal test data from center 1. The radiomic BM phenotype consisting of 8880 descriptive parameters per patient, which result from calculation of 296 radiomics features for each of the 30 BMS, was calculated for all patients. Exemplary cases demonstrated connections between typical BM patterns in MM and radiomic signatures of the respective BMS. In plausibility tests, predicted size and weight based on radiomics models of the radiomic BM phenotype significantly correlated with patients' actual size and weight ( P = 0.002 and P = 0.003, respectively). This pilot study demonstrates the feasibility of automatic, objective, comprehensive BM characterization from wb-MRI in multicentric data sets. This concept allows the extraction of high-dimensional phenotypes to capture the complexity of disseminated BM disorders from imaging. Further studies need to assess the clinical potential of this method for automatic staging, therapy response assessment, or prediction of biopsy results.