Artificial intelligence-based multi-omics analysis fuels cancer precision medicine.

With biotechnological advancements, innovative omics technologies are constantly emerging that have enabled researchers to access multi-layer information from the genome, epigenome, transcriptome, proteome, metabolome, and more. A wealth of omics technologies, including bulk and single-cell omics approaches, have empowered to characterize different molecular layers at unprecedented scale and resolution, providing a holistic view of tumor behavior. Multi-omics analysis allows systematic interrogation of various molecular information at each biological layer while posing tricky challenges regarding how to extract valuable insights from the exponentially increasing amount of multi-omics data. Therefore, efficient algorithms are needed to reduce the dimensionality of the data while simultaneously dissecting the mysteries behind the complex biological processes of cancer. Artificial intelligence has demonstrated the ability to analyze complementary multi-modal data streams within the oncology realm. The coincident development of multi-omics technologies and artificial intelligence algorithms has fuelled the development of cancer precision medicine. Here, we present state-of-the-art omics technologies and outline a roadmap of multi-omics integration analysis using an artificial intelligence strategy. The advances made using artificial intelligence-based multi-omics approaches are described, especially concerning early cancer screening, diagnosis, response assessment, and prognosis prediction. Finally, we discuss the challenges faced in multi-omics analysis, along with tentative future trends in this field. With the increasing application of artificial intelligence in multi-omics analysis, we anticipate a shifting paradigm in precision medicine becoming driven by artificial intelligence-based multi-omics technologies.

Prospective evaluation of quantitative response parameter in patients with Gastrointestinal Stroma Tumor undergoing tyrosine kinase inhibitor therapy-Impact on clinical outcome.

The purpose of this study was to determine if dual-energy CT (DECT) vital iodine tumor burden (ViTB), a direct assessment of tumor vascularity, allows reliable response assessment in patients with GIST compared to established CT criteria such as RECIST1.1 and modified Choi (mChoi). From 03/2014 to 12/2019, 138 patients (64 years [32-94 years]) with biopsy proven GIST were entered in this prospective, multi-center trial. All patients were treated with tyrosine kinase inhibitors (TKI) and underwent pre-treatment and follow-up DECT examinations for a minimum of 24 months. Response assessment was performed according to RECIST1.1, mChoi, vascular tumor burden (VTB) and DECT ViTB. A change in therapy management could be because of imaging (RECIST1.1 or mChoi) and/or clinical progression. The DECT ViTB criteria had the highest discrimination ability for progression-free survival (PFS) of all criteria in both first line and second line and thereafter treatment, and was significantly superior to RECIST1.1 and mChoi (p < .034). Both, the mChoi and DECT ViTB criteria demonstrated a significantly early median time-to-progression (both delta 2.5 months; both p < .036). Multivariable analysis revealed 6 variables associated with shorter overall survival: secondary mutation (HR = 4.62), polymetastatic disease (HR = 3.02), metastatic second line and thereafter treatment (HR = 2.33), shorter PFS determined by the DECT ViTB criteria (HR = 1.72), multiple organ metastases (HR = 1.51) and lower age (HR = 1.04). DECT ViTB is a reliable response criteria and provides additional value for assessing TKI treatment in GIST patients. A significant superior response discrimination ability for median PFS was observed, including non-responders at first follow-up and patients developing resistance while on therapy.

Early clearance of hairy cell leukaemia in the bone marrow after first-line treatment with cladribine predicts a favourable outcome.

First-line purine nucleoside analogues (PNAs) in hairy cell leukaemia (HCL) allow deep and long-lasting responses. We retrospectively analysed 53 HCL patients treated frontline with cladribine and assessed for response at 2 and 6 months after treatment to evaluate the kinetics of response. The estimated median progression-free survival was significantly different according to the degree of residual HCL infiltrate detected by immunohistochemistry at the bone marrow biopsy at 2 months (≤5% vs. >5%, 247 vs. 132 months, respectively, p = 0.033), but not at 6 months (p = 0.79). Our data suggest a favourable prognostic impact of early marrow HCL clearance in patients treated with cladribine.

Models using comprehensive, lesion-level, longitudinal [68Ga]Ga-DOTA-TATE PET-derived features lead to superior outcome prediction in neuroendocrine tumor patients treated with [177Lu]Lu-DOTA-TATE.

PURPOSE: Somatostatin receptor (SSTR) imaging features are predictive of treatment outcome for neuroendocrine tumor (NET) patients receiving peptide receptor radionuclide therapy (PRRT). However, comprehensive (all metastatic lesions), longitudinal (temporal variation), and lesion-level measured features have never been explored. Such features allow for capturing the heterogeneity in disease response to treatment. Furthermore, models combining these features are lacking. In this work we evaluated the predictive power of comprehensive, longitudinal, lesion-level 68GA-SSTR-PET features combined with a multivariate linear regression (MLR) model. METHODS: This retrospective study enrolled NET patients treated with [177Lu]Lu-DOTA-TATE and imaged with [68Ga]Ga-DOTA-TATE at baseline and post-therapy. All lesions were segmented, anatomically labeled, and longitudinally matched. Lesion-level uptake and variation in uptake were measured. Patient-level features were engineered and selected for modeling of progression-free survival (PFS). The model was validated via concordance index, patient classification (ROC analysis), and survival analysis (Kaplan-Meier and Cox proportional hazards). The MLR was benchmarked against single feature predictions. RESULTS: Thirty-six NET patients were enrolled and stratified into poor and good responders (PFS ≥ 25 months). Four patient-level features were selected, the MLR concordance index was 0.826, and the AUC was 0.88 (0.85 specificity, 0.81 sensitivity). Survival analysis led to significant patient stratification (p<.001) and hazard ratio (3⨯10-5). Lastly, in a benchmark study, the MLR modeling approach outperformed all the single feature predictors. CONCLUSION: Comprehensive, lesion-level, longitudinal 68GA-SSTR-PET analysis, combined with MLR modeling, leads to excellent predictions of PRRT outcome in NET patients, outperforming non-comprehensive, patient-level, and single time-point feature predictions. MESSAGE: Neuroendocrine tumor, peptide receptor radionuclide therapy, Somatostatin Receptor Imaging, Outcome Prediction, Treatment Response Assessment.

Treatment evaluation by volumetric segmentation in pediatric optic pathway glioma: evaluation of the effect of bevacizumab on intra-tumor components.

PURPOSE: Progressive pediatric optic pathway gliomas (OPGs) are treated by diverse systemic antitumor modalities. Refined insights on the course of intra-tumoral components are limited. METHODS: We performed an exploratory study on the longitudinal volumetric course of different (intra-)tumor components by manual segmentation of MRI at the start and after 3, 6 and 12 months of bevacizumab (BVZ) treatment. RESULTS: Thirty-one patients were treated with BVZ (median 12 months, range: 2-39 months). During treatment the total tumor volume decreased with median 19.9% (range: - 62.3 to + 29.7%; n = 30) within the first 3 months, decreased 19.0% (range: - 68.8 to + 96.1%; n = 28) between start and 6 months and 27.2% (range: -73.4 to + 36.0%; n = 21) between start and 12 months. Intra-tumoral cysts were present in 12 OPGs, all showed a decrease of volume during treatment. The relative contrast enhanced volume of NF1 associated OPG (n = 11) showed an significant reduction compared to OPG with a KIAA1549-BRAF fusion (p < 0.01). Three OPGs progressed during treatment, but were not preceded by an increase of relative contrast enhancement. CONCLUSION: Treatment with BVZ of progressive pediatric OPGs leads to a decrease of both total tumor volume and cystic volume for the majority of OPGs with emphasis on the first three months. NF1 and KIAA1549-BRAF fusion related OPGs showed a different (early) treatment effect regarding the tumor enhancing component on MRI, which did not correlate with tumor volume changes. Future research is necessary to further evaluate these findings and its relevance to clinical outcome parameters.

Multidisciplinary Decision-Making-ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study).

PURPOSE OF REVIEW: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments. RECENT FINDINGS: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved.

Machine learning-based response assessment in patients with rectal cancer after neoadjuvant chemoradiotherapy: radiomics analysis for assessing tumor regression grade using T2-weighted magnetic resonance images.

PURPOSE: This study aimed to assess tumor regression grade (TRG) in patients with rectal cancer after neoadjuvant chemoradiotherapy (NCRT) through a machine learning-based radiomics analysis using baseline T2-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: In total, 148 patients with locally advanced rectal cancer(T2-4 or N+) who underwent MR imaging at baseline and after chemoradiotherapy between January 2010 and May 2021 were included. A region of interest for each tumor mass was drawn by a radiologist on oblique axial T2-weighted images, and main features were selected using principal component analysis after dimension reduction among 116 radiomics and three clinical features. Among eight learning models that were used for prediction model development, the model showing best performance was selected. Treatment responses were classified as either good or poor based on the MR-assessed TRG (mrTRG) and pathologic TRG (pTRG). The model performance was assessed using the area under the receiver operating curve (AUROC) to classify the response group. RESULTS: Approximately 49% of the patients were in the good response (GR) group based on mrTRG (73/148) and 26.9% based on pTRG (28/104). The AUCs of clinical data, radiomics models, and combined radiomics with clinical data model for predicting mrTRG were 0.80 (95% confidence interval [CI] 0.73, 0.87), 0.74 (95% CI 0.66, 0.81), and 0.75(95% CI 0.68, 0.82), and those for predicting pTRG was 0.62 (95% CI 0.52, 0.71), 0.74 (95% CI 0.65, 0.82), and 0.79 (95% CI 0.71, 0.87). CONCLUSION: Radiomics combined with clinical data model using baseline T2-weighted MR images demonstrated feasible diagnostic performance in predicting both MR-assessed and pathologic treatment response in patients with rectal cancer after NCRT.

RAPNO efforts in Brain Tumour Outcomes.

Assessing treatment efficacy for brain tumours has evolved since its inception with the introduction of MacDonald's criteria, which pioneered the utility of imaging to determine an objective and quantifiable response to treatment. This criterion failed to distinguish pseudo response or progression from progression and did not account for non-enhancing disease therefore; the response assessment in neuro-oncology (RANO) working group was established to account for these limitations. Since, its commencement it has worked to determine response assessment for multiple tumours. As paediatric tumours exhibit heterogeneous and variable-enhancing characteristics, the response assessment in paediatric neuro-oncology (RAPNO) working group was formed to create separate criteria. Six response criteria have been published to date, and the article summarizes them.

Meta-Analysis of 49 Roche Oncology Trials Comparing Blinded Independent Central Review (BICR) and Local Evaluation to Assess the Value of BICR.

BACKGROUND: Blinded independent central review (BICR) of radiographic images is frequently conducted in oncology trials to address the potential bias of local evaluation (LE) of endpoints such as progression-free survival (PFS) and objective response rate (ORR). Given that BICR is a complex and costly process, we evaluated the agreement between LE- and BICR-based treatment effect results and the impact of BICR on regulatory decision-making. MATERIALS AND METHODS: Meta-analyses were performed using hazard ratios (HRs) for PFS and odds ratios (ORs) for ORR from all randomized Roche-supported oncology clinical trials during 2006-2020 that had both LE and BICR results (49 studies with a total of over 32 000 patients). RESULTS: Overall, the evaluation bias of LE overestimating the treatment effect compared with BICR based on PFS was numerically small and not clinically meaningful, especially for double-blind studies (HR ratio between BICR and LE: 1.044). A larger bias is more likely to occur in studies with open-label design, smaller sample sizes, or an unequal randomization ratio. The majority (87%) of the PFS comparisons led to the same statistical inference by BICR and LE. For ORR, a high degree of agreement between BICR and LE results was also observed (OR ratio of 1.065), although the agreement was slightly lower than for PFS. CONCLUSION: BICR did not notably impact the study interpretation nor drive the sponsor's regulatory submission decisions. Hence, if bias can be diminished by appropriate means, LE is deemed as reliable as BICR for certain study settings.

Prognostic utility of RECIP 1.0 with manual and AI-based segmentations in biochemically recurrent prostate cancer from [68Ga]Ga-PSMA-11 PET images.

PURPOSE: This study aimed to (i) validate the Response Evaluation Criteria in PSMA (RECIP 1.0) criteria in a cohort of biochemically recurrent (BCR) prostate cancer (PCa) patients and (ii) determine if this classification could be performed fully automatically using a trained artificial intelligence (AI) model. METHODS: One hundred ninety-nine patients were imaged with [68Ga]Ga-PSMA-11 PET/CT once at the time of biochemical recurrence and then a second time a median of 6.0 months later to assess disease progression. Standard-of-care treatments were administered to patients in the interim. Whole-body tumour volume was quantified semi-automatically (TTVman) in all patients and using a novel AI method (TTVAI) in a subset (n = 74, the remainder were used in the training process of the model). Patients were classified as having progressive disease (RECIP-PD), or non-progressive disease (non RECIP-PD). Association of RECIP classifications with patient overall survival (OS) was assessed using the Kaplan-Meier method with the log rank test and univariate Cox regression analysis with derivation of hazard ratios (HRs). Concordance of manual and AI response classifications was evaluated using the Cohen's kappa statistic. RESULTS: Twenty-six patients (26/199 = 13.1%) presented with RECIP-PD according to semi-automated delineations, which was associated with a significantly lower survival probability (log rank p < 0.005) and higher risk of death (HR = 3.78 (1.96-7.28), p < 0.005). Twelve patients (12/74 = 16.2%) presented with RECIP-PD according to AI-based segmentations, which was also associated with a significantly lower survival (log rank p = 0.013) and higher risk of death (HR = 3.75 (1.23-11.47), p = 0.02). Overall, semi-automated and AI-based RECIP classifications were in fair agreement (Cohen's k = 0.31). CONCLUSION: RECIP 1.0 was demonstrated to be prognostic in a BCR PCa population and is robust to two different segmentation methods, including a novel AI-based method. RECIP 1.0 can be used to assess disease progression in PCa patients with less advanced disease. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000608561) on 11 June 2015.

Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients.

PURPOSE: The aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival. METHODS: This retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2-9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP). RESULTS: After one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1-5) and 2 (1-6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09). CONCLUSION: In this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.

Predictive value on advance hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial.

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Treatment Response Assessment in Multiple Myeloma: Histogram Analysis of Total Tumor Apparent Diffusion Coefficient based on Whole-body Diffusion-weighted MR Imaging.

BACKGROUND: The International Myeloma Working Group (IMWG) consensus criteria for response assessment in multiple myeloma (MM) has methodological limitations. Whole-body diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) histogram analysis may be complementary to response assessment of MM. PURPOSE: To explore the role of histogram analysis of the ADC based on the total tumor volume (ttADC) in response assessment in patients with newly diagnosed MM (NDMM). STUDY TYPE: Retrospective. POPULATION: Thirty-six patients with NDMM. FIELD STRENGTH/SEQUENCE: 3.0T/single-shot DWI echo planar imaging (EPI) sequence with an integrated slice-by-slice shimming (iShim) technique. ASSESSMENT: Baseline (median: 1 day before treatment) and post-treatment (median: five cycles of therapy) whole-body DWI were analyzed. A region of interest (ROI) containing lesions on every section of baseline image was drawn to derive the per-patient total tumor data. Post-treatment image analysis was based on the same ROI as the corresponding baseline. Histogram metrics were extracted from both ROIs. Patients were categorized into the very good partial response or better (VGPR+) group and the less than VGPR group per the IMWG response criteria for response assessment. Progression-free survival (PFS) was also calculated. STATISTICAL TESTS: Mann-Whitney test and Fisher's exact or Chi-squared tests, Receiver operating characteristic (ROC) analysis and DeLong test, Kaplan-Meier analysis and Cox proportional hazards model. A two-tailed P-value <0.05 was considered statistically significant. RESULTS: Thirty patients were categorized into the VGPR+ group and six into the less than VGPR group. The ttADC histogram changes between post-treatment and baseline metrics (ΔttADC) revealed significant differences in all percentile values between the VGPR+ and less than VGPR groups. For distinguishing VGPR+, ΔttADC_5th percentile had the largest area under the curve (AUC) (0.950, 95% CI 0.821-0.995). Patients with lower ΔttADC_5th percentile values (cutoff point, 188.193) showed significantly longer PFS (HR = 34.911, 95% CI 6.392-190.677). DATA CONCLUSION: ttADC histogram may facilitate response assessment in patients with NDMM. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.

Updates on LI-RADS Treatment Response Criteria for Hepatocellular Carcinoma: Focusing on MRI.

As the incidence of hepatocellular carcinoma (HCC) and subsequent treatments with liver-directed therapies rise, the complexity of assessing lesion response has also increased. The Liver Imaging Reporting and Data Systems (LI-RADS) treatment response algorithm (LI-RADS TRA) was created to standardize the assessment of response after locoregional therapy (LRT) on contrast-enhanced CT or MRI. Originally created based on expert opinion, these guidelines are currently undergoing revision based on emerging evidence. While many studies support the use of LR-TRA for evaluation of HCC response after thermal ablation and intra-arterial embolic therapy, data suggest a need for refinements to improve assessment after radiation therapy. In this manuscript, we review expected MR imaging findings after different forms of LRT, clarify how to apply the current LI-RADS TRA by type of LRT, explore emerging literature on LI-RADS TRA, and highlight future updates to the algorithm. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Towards the definition of progressive disease in brain metastasis treated with laser ablation: an evidence-based study.

PURPOSE: The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggest that a 20% increase in size of brain metastasis (BM) assessed in 6-12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyze which tumor volume variations were associated with LP. METHODS: We analyzed 40 BM that underwent LITT between 2013 and 2022. For this study, LP was defined following radiographic features. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. RESULTS: Out of 40 lesions, 12 (30%) had LP. An increase in volume of 25.6% from baseline within 120-180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.041). The multivariate analysis showed a 25% increase in volume between 120 and 180 days as a negative predictive factor (p = 0.02). Volumetric changes within 60-90 days after LITT did not predict LP (AUC: 0.57; p = 0.61). CONCLUSION: Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

Potential clinical utility of 68Ga-DOTATATE PET/CT for detection and response assessment in cardiac sarcoidosis.

BACKGROUND: Somatostatin receptor is expressed in sarcoid granulomas, and preliminary clinical studies have shown that myocardial sarcoidosis can be identified on somatostatin receptor-targeted PET. We examined the potential clinical use of 68Ga-DOTATATE PET/CT for diagnosis and response assessment in cardiac sarcoidosis compared to 18F-FDG PET/CT. METHODS: Eleven cardiac sarcoidosis patients with 18F-FDG PET/CT were prospectively enrolled for cardiac 68Ga-DOTATATE PET/CT. The two PET/CT studies were interpreted independently and were compared for patient-level and segment-level concordance, as well as for the degree of radiotracer uptake. Follow-up 68Ga-DOTATATE PET/CT was performed in eight patients. RESULTS: Patient-level concordance was 91%: ten patients had multifocal DOTATATE uptake (active cardiac sarcoidosis) and one patient showed diffuse DOTATATE uptake. Segment-level agreement was 77.1% (Kappa 0.53 ± 0.07). The SUVmax-to-blood pool ratio was lower on 68Ga-DOTATATE PET/CT (3.2 ± 0.6 vs. 4.9 ± 1.5, P = 0.006 on paired t test). Follow-up 68Ga-DOTATATE PET/CT showed one case of complete response and one case of partial response, while 18F-FDG PET/CT showed four cases of response, including three with complete response. CONCLUSION: Compared to 18F-FDG PET/CT, 68Ga-DOTATATE PET/CT can identify active cardiac sarcoidosis with high patient-level concordance, but with moderate segment-level concordance, low signal-to-background ratio, and underestimation of treatment response.

Imaging Follow-Up of Nonsurgical Therapies for Lung Cancer: AJR Expert Panel Narrative Review.

Lung cancer continues to be the most common cause of cancer-related death worldwide. In the past decade, with the implementation of lung cancer screening programs and advances in surgical and nonsurgical therapies, the survival of patients with lung cancer has increased, as has the number of imaging studies that these patients undergo. However, most patients with lung cancer do not undergo surgical re-section, because they have comorbid disease or lung cancer in an advanced stage at diagnosis. Nonsurgical therapies have continued to evolve with a growing range of systemic and targeted therapies, and there has been an associated evolution in the imaging findings encountered at follow-up examinations after such therapies (e.g., with respect to posttreatment changes, treatment complications, and recurrent tumor). This AJR Expert Panel Narrative Review describes the current status of nonsurgical therapies for lung cancer and their expected and unexpected imaging manifestations. The goal is to provide guidance to radiologists regarding imaging assessment after such therapies, focusing mainly on non-small cell lung cancer. Covered therapies include systemic therapy (conventional chemotherapy, targeted therapy, and immunotherapy), radiotherapy, and thermal ablation.

Disease Assessments in Patients with Glioblastoma.

PURPOSE OF REVIEW: The neuro-oncology team faces a unique challenge when assessing treatment response in patients diagnosed with glioblastoma. Magnetic resonance imaging (MRI) remains the standard imaging modality for measuring therapeutic response in both clinical practice and clinical trials. However, even for the neuroradiologist, MRI interpretations are not straightforward because of tumor heterogeneity, as evidenced by varying degrees of enhancement, infiltrating tumor patterns, cellular densities, and vasogenic edema. The situation is even more perplexing following therapy since treatment-related changes can mimic viable tumor. Additionally, antiangiogenic therapies can dramatically decrease contrast enhancement giving the false impression of decreasing tumor burden. Over the past few decades, several approaches have emerged to augment and improve visual interpretation of glioblastoma response to therapeutics. Herein, we summarize the state of the art for evaluating the response of glioblastoma to standard therapies and investigational agents as well as challenges and future directions for assessing treatment response in neuro-oncology. RECENT FINDINGS: Monitoring glioblastoma responses to standard therapy and novel agents has been fraught with many challenges and limitations over the past decade. Excitingly, new promising methods are emerging to help address these challenges. Recently, the Response Assessment in Neuro-Oncology (RANO) working group proposed an updated response criteria (RANO 2.0) for the evaluation of all grades of glial tumors regardless of IDH status or therapies being evaluated. In addition, advanced neuroimaging techniques, such as histogram analysis, parametric response maps, morphometric segmentation, radio pharmacodynamics approaches, and the integrating of amino acid radiotracers in the tumor evaluation algorithm may help resolve equivocal lesion interpretations without operative intervention. Moreover, the introduction of other techniques, such as liquid biopsy and artificial intelligence could complement conventional visual assessment of glioblastoma response to therapies. Neuro-oncology has evolved over the past decade and has achieved significant milestones, including the establishment of new standards of care, emerging therapeutic options, and novel clinical, translational, and basic research. More recently, the integration of histopathology with molecular features for tumor classification has marked an important paradigm shift in brain tumor diagnosis. In a similar manner, treatment response monitoring in neuro-oncology has made considerable progress. While most techniques are still in their inception, there is an emerging body of evidence for clinical application. Further research will be critically important for the development of impactful breakthroughs in this area of the field.

The Crying Need for a Better Response Assessment in Rectal Cancer.

OPINION STATEMENT: Since total neoadjuvant treatment achieves almost 30% pathologic complete response, organ preservation has been increasingly debated for good responders after neoadjuvant treatment for patients diagnosed with rectal cancer. Two organ preservation strategies are available: a watch and wait strategy and a local excision strategy including patients with a near clinical complete response. A major issue is the selection of patients according to the initial tumor staging or the response assessment. Despite modern imaging improvement, identifying complete response remains challenging. A better selection could be possible by radiomics analyses, exploiting numerous image features to feed data characterization algorithms. The subsequent step is to include baseline and/or pre-therapeutic MRI, PET-CT, and CT radiomics added to the patients' clinicopathological data, inside machine learning (ML) prediction models, with predictive or prognostic purposes. These models could be further improved by the addition of new biomarkers such as circulating tumor biomarkers, molecular profiling, or pathological immune biomarkers.

Endoscopy and MRI for restaging early rectal cancer after neoadjuvant treatment.

AIM: Chemoradiotherapy (CRT) has great potential to downstage rectal cancer. Response assessment has been investigated in locally advanced rectal cancer but not in early stage rectal cancer. The aim is to characterize the diagnostic accuracy of endoscopy performed by surgical endoscopists compared to (diffusion-weighted, DWI) MRI only and a multimodal approach combining (DWI-)MRI and endoscopic information both analysed by an abdominal radiologist for response assessment in early rectal cancer after neoadjuvant CRT. MATERIALS AND METHODS: Patients treated with neoadjuvant CRT for early distal rectal cancer (cT1-3 N0) followed by transanal endoscopic microsurgery were included. Three separate reassessment groups were analysed for response assessment using endoscopic evaluation alone versus (DWI-)MRI alone versus the combination of endoscopy with (DWI-)MRI with a focus on sensitivity and specificity and analysis using receiver operating characteristic curves. RESULTS: Three cohorts (N = 36, N = 25 and N = 25, respectively) were analysed for response assessment. Of the endoscopy cohort, 16 of the 36 patients had a complete response. Area under the curve was 0.69 (0.66-0.74; pooled sensitivity 55.3%, pooled specificity 80.0%). Agreement for scoring separate endoscopic features was poor to moderate. Of the (DWI-)MRI cohort, 11 of the 25 patients had a complete response. Area under the curve for (DWI-)MRI alone was 0.55 (sensitivity 72.7%, specificity 42.9%). The areas under the receiver operating characteristic curve improved to 0.68 (sensitivity 90.9%, specificity 75.0%) when (DWI-)MRI was combined with endoscopic information, with 11 out of 25 patients with a complete response. The most accurate response assessment was made by combining endoscopy and (DWI-)MRI with a high negative predictive value (90.9%). CONCLUSION: Good and complete responders after chemoradiation of early stage rectal cancer can be best assessed using a multimodality approach combining endoscopy and (DWI-)MRI.