RPS 116 - Staging, metastases and response assessment

Author Block: R. F. Valenzuela, B. Amini, E. Duran-Sierra, J. E. Madewell, M. Canjirathinkal, C. M. Costelloe, W. Murphy; Houston, TX/US
Purpose: Undifferentiated pleomorphic sarcoma (UPS) is the largest soft-tissue sarcoma subgroup. Post-therapeutically, UPS demonstrates hemosiderin deposition, fibrosis, and calcification. This study aimed to establish the clinical value of multiparametric MRI (mpMRI) for predicting UPS response.
Methods or Background: An IRB-approved retrospective study included 33 extremity UPS patients with pre-operative mpMRI, including diffusion-weighted imaging (DWI), contrast-enhanced susceptibility-weighted imaging (CE-SWI), and perfusion-weighted imaging with dynamic contrast-enhancement (PWI/DCE), and surgical resection February 2021-May 2023. Lesions were visually classified on CE-SWI into one of 6 morphology patterns. On PWI/DCE, lesions were classified into one of 6 patterns, and time-intensity curves (TICs) were classified as types I-V. Patients were divided into three groups based on the percentage of pathology-assessed treatment effect (PATE) in the surgical specimen: Responders (>=90% PATE, n=16), partial-responders (31-89% PATE, n=10), and non-responders (<=30% PATE, n=7). Receiver operating characteristic (ROC) analysis of classification models based on CE-SWI and PWI/DCE patterns and TICs compared responders vs. partial/non-responders.
Results or Findings: At post-radiation therapy (PRT), a CE-SWI Complete Ring pattern was observed in 71% of responders (p=7.71x10-6). On PWI/DCE images, 79% of responders displayed a Capsular pattern (p=1.49x10-7), and 100% demonstrated a TIC-type II (p=8.32x10-7).
RECIST could not separate responders from partial/non-responders; all demonstrated 100% stability at PRT and pseudoprogression at PC.
ROC analysis comparing responders (n=14) vs. partial/non-responders (n=16) at PRT showed that the model combining the PWI/DCE TIC-type II, PWI/DCE Capsular pattern and CE-SWI Complete Ring pattern yielded the highest classification performance (AUC=0.99).
Conclusion: mpMRI-derived features can help assess UPS treatment response. Observing a pre-operative PWI/DCE TIC-type II, PWI/DCE Capsular pattern, and CE-SWI Complete Ring pattern can potentially predict successfully treated UPS patients with >=90% PATE, outperforming RECIST.
Limitations: Limitations include a small sample (n=33) and manual, time-consuming tumor VOI segmentation.
Funding for this study: The John S. Dunn, Sr. Distinguished Chair in Diagnostic Imaging.
M.R Evelyn Hudson Foundation Endowed Professorship.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: Not applicable

Author Block: A. Vanzulli, R. Vigorito, C. Buonomenna, P. Verderio, S. Pasquali, P. G. Casali, C. Morosi, S. Stacchiotti, A. Gronchi; Milan/IT
Purpose: We report the results of the pre-planned secondary analysis of radiologic responses (RR) of ISG-STS 1001, a randomized clinical trial comparing anthracycline + ifosfamide (AI) vs. histology-tailored (HT) neoadjuvant chemotherapy for primary localized high-risk soft-tissue sarcomas of the extremities/trunk wall.
Methods or Background: Patients with undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma (LMS), malignant peripheral nerve sheath tumor, synovial sarcoma or myxoid liposarcoma (MLPS) were randomized, whereas patients with myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma or unclassified sarcoma were allocated in the observational arm (O) and treated with AI.
Patients with UPS, LMS or MLPS needing concurrent preoperative radiotherapy were included in O.
We evaluated associations between: Disease-Free Survival (DFS)/Overall Survival (OS) and centrally reviewed RR, assessed with RECIST 1.1 and as percent dimensional variation (D; both dichotomized and continuous); DFS/OS and histology; RR and histology.
Results or Findings: 435 patients were included (287 randomized, 148 observed).
The analysis of RR comprised 236 patients (154 randomized, 82 observed) with measurable disease and available for central review.
RECIST best responses were: 28 (11.9%) partial response (PR), 195 (82.6%) stable disease (SD) and 13 (5.5%) progressive disease (PD).
RECIST significantly correlated with DFS (PD-vs-PR: HR 8.18, 95% CI 2.96-22.58; SD-vs-PR: HR 2.96, 95% CI 1.30-6.75) and OS (PD-vs-PR: HR 12.61, 95% CI 3.40-46.84; SD-vs-PR: HR 4.24, 95% CI 1.34-13.47).
The median value of D was -1.6%. Patients with D > -1.6% had worse clinical outcomes than those with D < -1.6% (DFS: HR 1.73, 95% CI 1.19-2.50; OS: HR 1.86, 95% CI 1.21-2.86).
D in continuous scale inversely correlated with DFS (HR 1.53, 95% CI 1.25-1.87) and OS (HR 1.78, 95% CI 1.41-2.25).
Conclusion: Dimensional variation in continuous scale predicted the proportional efficacy of treatment irrespective of tumor histology.
Limitations: Nothing to disclose.
Funding for this study: Pharmamar® provided trabectedin for the HG-MLPS cohort.
The study was partially funded through a European Union grant (EUROSARC FP7 278472). In addition, the French sites were supported by NETSARC, LYRICAN (LYRICAN [INCA-DGOS-INSERM 12563]) and DEPGYN (RHU4).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The trial protocol and all amendments were approved by the independent ethics committee at each trial center.

Author Block: N. Magdi, M. Elmansy, M. Elhawary, A. Sultan; Mansoura/EG
Purpose: Our study was conducted to elucidate the role of the T2-Dixon sequence as a rapid alternative to the standard Whole-body magnetic resonance imaging (WB-MRI) protocol with the assessment of its diagnostic accuracy and comparability to the established methodology.
Methods or Background: This prospective study included 30 patients with primary solid malignancies who underwent WB-MRI. The sequences obtained were T1WI, STIR, and T2-Dixon (fat-only and water-only images). Skeletal metastases were evaluated in each sequence. Results were compared between the T1-STIR combination and T2-Dixon fat and water reconstructions.
Results or Findings: The sensitivity of fat and water reconstructions from a single T2-Dixon in the detection of lytic skeletal metastases was marginally superior to a combination of T1WI and STIR sequences (0-7%). Detection of mixed lesions demonstrated equally high sensitivity in both protocols. Sclerotic metastases detection in WB-MRI showed low sensitivity in both protocols. However, specificity surpassed 95% for all lesion types in both protocols. Overall image quality was favored (in 87-90% of patients ) in T2-Dixon images. The overall estimated acquisition timing using T2-Dixon appeared to be approximately half that of the standard T1-STIR combination.
Conclusion: WB-MRI using T2-Dixon fat and water reconstructions showed similar accuracy to T1WI and STIR combination in the evaluation of skeletal metastases in patients with primary solid cancers with significantly shorter acquisition time.
Limitations: Few skull and humeri lesions with limited assessment of the sclerotic lesions due to high fals negative results.
Lack of quantitative analysis of signal to noise and contrast to noise ratio.
Funding for this study: No funding
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Research Ethics Committee of the Faculty of Medicine at Mansoura University in Egypt on 10 /1 /2023; reference number of approval: MS.22.12.2250

Author Block: P. Chapellier¹, S. W. Soo², O. Westerland², A. Green², S. Gourtsoyianni³, V. Goh²; ¹Lausanne/CH, ²London/UK, ³Athens/GR
Purpose: Whole-body MRI (WB-MRI) may be valuable alternative to standard imaging pathways for staging. We evaluated how reader experience impacts agreement for tumour-node-metastasis (TNM) staging of oesophageal cancer.
Methods or Background: Following ethical approval, prospective patients underwent WB-MRI (T2-weighted, diffusion-weighted, T1-weighted post-contrast) alongside standard imaging (contrast-enhanced CT, 18F-FDG PET/CT ± EUS). WB-MRI was staged using AJCC TNMv8 by four readers from different countries with different levels of experience: subspecialty vs. non-subspecialty trained; in-training vs. staff radiologists. Inter-reader agreement was assessed using kappa statistics. For each reader, agreement with a reference standard of final tumour board stage, surgical pathology and clinical follow up was obtained.
Results or Findings: 29/30 (97%) patients had adenocarcinoma; 25/30 (83%) had ≥T3 stage; 27/30 (90%) had locoregional lymphadenopathy; 12/30 (40%) were metastatic. 22/30 (74%) received chemotherapy only; 8/30 (27%) had surgery, 63% with neoadjuvant treatment.

Compared to reference standard, agreement for T- and N-stage was highest for the two gastrointestinal-trained radiologists (T-stage: κ =0.516, κ =0.824; N-stage: κ =0.434, κ =0.589, respectively). Agreement for M-stage was highest for the oncology-trained radiologist (κ =0.795). Detection of lung metastases was limited on MRI.

Inter-reader agreement was also highest for gastrointestinal-trained radiologists (T-stage: κ = 0.624; N-stage: κ = 0.822). Agreement across TNM staging was lowest with the in-training radiologist who had no exposure to WB-MRI staging.
Conclusion: WB-MRI could be valuable alternative for initial TNM staging of oesophageal cancer, but reliable interpretation appears to be related to subspecialty experience and level of training.
Limitations: WB-MRI was a relatively long acquisition, and not suit all patients.
Nodal disease was not just based on size measurement.
MRI is limited for some sites eg.lung
Funding for this study: This project was supported by the National Institute for Health and Care Research (MIHR) Biomedical Research Centre at Guy’s & St Thomas’ Hospitals and King’s College London.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study was approved by the Research Ethics Committee (IRAS ID 107508, 12/LO/1754).

Author Block: C. Sattin¹, C. Pizzi¹, M. Kosmin², W. Mcguire³, A. Makris², N. J. Taylor², G. Petralia¹, A. R. R. Padhani³; ¹Milan/IT, ²London/UK, ³Northwood/UK
Purpose: To document inter- and intra-observer variability and test-retest reproducibility of quantitative MRI metastasis biomarkers.
Methods or Background: Whole-body MRI was performed in women with bone-predominant metastatic breast cancer on a 1.5T MRI system. Paired reproducibility scans were done in 14 patients after repositioning. Observer variability was assessed in 10 patients after a two-week washout period.
Two trained radiologists delineated up to 5 bone metastases per patient. Quantitative biomarkers (lesion sizes, apparent diffusion coefficient (ADC), relative fat fraction (rFF%) and b-900 s/mm2 signal-to-muscle ratio [SMR]) for each lesion were averaged per patient.
Data logn transformed after testing for normality. Within-patient coefficient of variation (wCV) and variance ratio were calculated. The repeatability (R-value; mean 95% confidence) for a single patient was calculated.
Results or Findings: Reproducibility analysis (2 radiologist consensus; 14 patients; 41 lesions): Variance ratios were >15 for all biomarkers. Size had wCV of 3.5% and R-value of 9.5%; SMR had wCV of 7.4% and R-value of 19.8%; ADC had wCV of 2% and R-value of 5.2%; rFF% had wCV of 9.4% and R-value of 24.9%. Inter- and intra-observer variability (for 2 independent radiologists; 10 patients; different lesions) were similar (ICC >0.8) indicating consistent reader performance.
Conclusion: Higher reproducibility test variance ratios and interclass correlations of clinically relevant biomarkers indicate the reliability of radiological assessments regardless of the observer. Changes in aggregated lesion size of >3mm, SMR of > 1.4 au, ADC of >53 µm2/s and rFF% of > 2.7% can be used as bone tumour response biomarkers in women with metastatic breast cancer.
Limitations: This abstract represents a preliminary part of a larger study that aims to evaluate whether changes in quantitative and qualitative WB-MRI biomarkers could be predictive of outcomes in patients with bone-predominant MBC on SACT.
Funding for this study: This work was funded by the Paul Strickland Scanner Centre Charity (UK registered charity number 298867) and the Fighting Breast Cancer (UK registered charity number 1091882).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: All procedures permorfed in this study (ClinicalTrials.gov identifier: NCT03266744) followed the ethical standards of the National Health Service Health research Authority East of England-Cambridge East Research Committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Author Block: C. Nelles, P. Rauen, T. M. Dratsch, D. Maintz, J. Kottlors, N. Große Hokamp, D. Zopfs, T. Persigehl, S. Lennartz; Cologne/DE
Purpose: To investigate the sensitivity, specificity and qualitative assessment of spectral image reconstructions for metastases in melanoma patients in a large-scale, multi-reader evaluation.
Methods or Background: In total, 308 patients with melanoma, 95 patients with metastases and a control group of 213 patients without metastases, who underwent staging CT of the chest and abdomen on a dual-layer dual-energy CT system (dlDECT) were retrospectively included. Conventional images (CI), iodine overlays (IO) and virtual monoenergetic images at 40 keV (VMI40keV) were reconstructed. Six radiologists (three experienced, three less experienced) evaluated all cases in a CI-based session and a session based on a combination of CI, IO and VMI40keV. Readers were asked to binarily determine presence of metastases in specific tissues and to indicate diagnostic certainty and lesion delineation on 5-point Likert scales.
Results or Findings: Sensitivity for detection of metastases in skeletal muscle and peritoneum was significantly higher for the spectral assessment (for skeletal muscle 70% vs. 61%; for peritoneum 76% vs. 62%, both: p < 0.05). For subcutaneous metastases, there was a significant increase in specificity (92% vs. 89%, p < 0.05), however accompanied with a significant decrease in sensitivity (79% vs. 85%, p < 0.05). Diagnostic certainty was rated significantly higher for spectral images than CI for 100% (6/6) of the assessed tissues, whereas improvements in lesion delineation were noted for skeletal muscle, subcutaneous tissue and pancreas.
Conclusion: In melanoma patients, the benefit of dlDECT-derived spectral reconstructions depends on the assessed tissue. While assessment of skeletal muscle and peritoneal metastases was significantly improved, low or absent iodine uptake of subcutaneous lesions led to false negatives and a consecutive decrease in sensitivity.
Limitations: -Retrospective, monocenter study design
-The results may not be generalisable to all different DECT platforms
Funding for this study: Funding was provided by the German Research Foundation (DFG, FI 773/15-1).
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: After reviewing the study design, the institutional review board waived the need for informed patient consent for this retrospective single-center study.

Author Block: A. Keane¹, H. Takahashi², C. Zhang³, C. Thiels², P. Navin²; ¹Dublin/IE, ²Rochester, MN/US, ³Pheonix, AZ/US
Purpose: Small bowel neuroendocrine neoplasms (sbNENs) provide challenges in diagnosis and management. Current gold standard treatment is open resection with manual small bowel palpation as 45-50% of sbNEN have synchronous lesions. Advancements in nuclear medicine have improved preoperative assessment, potentially negating manual palpation and allowing for laparoscopic approach. DOTATATE PET CT (DPCT) and PET MR can identify somatostatin receptors, frequently expressed on sbNENs. We aim to assess the accuracy of DPCT versus PET MR in determining multifocality of sbNENs.
Methods or Background: Multicentre retrospective analysis was performed on patients with sbNEN who underwent open small bowel resection between January 2016 to August 2022 and had either preoperative DPCT or PET MR. Blinded retrospective review of images for small bowel lesions was performed by two fellowship-trained radiologists and compared to postoperative pathology reports. Final radiology diagnosis was attained by consensus agreement. Descriptive statistics, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operator characteristic curve (AUROC) of DPCT and PET MR were compared.
Results or Findings: Seventy-eight patients met inclusion criteria. Fifty-six (71.8%) had preoperative DPCT, twenty-two (28.2%) had PET MR. Forty-eight patients (61.5%) had multiple (> 1)sbNENs on final pathology. Thirty-six (75.0%) were identified on preoperative imaging. DPCT and PET MR demonstrated sensitivity of 85.0% and 58.0% respectively, specificity of 81.0% and 60.0%, PPV of 87.9% and 63.6%, NPV of 77.3% and 54.6%, and accuracy of 83.6% and 59.0% for the presence of multifocal disease. AUROC was 0.8 for DPCT and 0.5 for PET MR.
Conclusion: DPCT demonstrated higher accuracy in identifying multifocal sbNEN versus PET MR. However, as the NPV is insufficient, we conclude that preoperative DPCT should not replace open exploration.
Limitations: Retrospective study, underpowered due to rarity of sbNENs.
Funding for this study: Nil
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: IRB (Institutional Review Board)

Author Block: H. Beaumont¹, R. Gill², N. Faye¹, A. Iannessi¹; ¹Valbonne/FR, ²Boston, MA/US
Purpose: In lung cancer trials, blinded independent central response assessment with double reads is challenging and prone to interobserver variability. We analyzed the patterns of discordance in reporting Progressive Disease (PD) and performed a root cause analysis.
Methods or Background: We retrospectively analyzed data from five clinical trials evaluating 1932 lung cancer patients treated with targeted and immune therapies, read by 17 central readers. Progressive Disease was defined based on RECIST 1.1 criteria. The RECIST components were the Sum of tumors Diameter (SOD), the unequivocal progression of the non-Target Lesions (NTL) and the detection of New Lesion (NL).
We analyzed the RECIST components according to 1) Concordant/discordant PD detection; 2) Positive Predictive Value (PPV) of declaring PD; 3) Offset versus single reader detection.
Results or Findings: Discordance in PD was observed in 39.2% (675/1718) of patients, with adjudication of PD for 62.5% (422/675) based on 44.8% (95%CI: 39.9, 49.8) new lesion detection, 28.3% (95%CI: 24.0, 33.0) significant increase of SOD and 12.6% (95%CI: 9.5, 16.2) unequivocal non-target progression. For 54.2% of concordant PD, at least one reader involved more than one RECIST component. The PPV for increased SOD was 0.59, rising to 0.89 when multiple RECIST components were involved.
In 49.2% of discrepant cases, PD was reported with a delay of one cycle in majority of cases (80%). Confirmation rate for NLs in the lungs was lowest (40.6%) and new nodal lesions was highest (88.4%).
Conclusion: Discordance among trained central readers in lung cancer trials is common. New lesion detection is pivotal in the detection of PD, also the main cause of discordances. Involving multiple RECIST components improves the reliability of assessments. When relying on NL only, the detection of extra pulmonary lesion is more reliable.
Limitations: No limitations
Funding for this study: No funding
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: Median Technologies institutional ethics committee approved the study, informed consent was not required for this retrospective analysis

Author Block: N. Plakhotina, A. V. Smirnova, K. Boiko, V. Bikulov, P. Ivanov; Saint-Petersburg/RU
Purpose: To develop a diagnostic algorithm and identify imaging patterns for metastatic abdominal lesions in children with brain tumors following shunt placement.
Methods or Background: Clinical cases of shunt-associated metastasis of primary brain tumors in children, identified through CT, MRI, and laparoscopy, with morphological confirmation.
Results or Findings: Acute abdominal pain developed in children with embryonal tumors (2 patients with medulloblastoma, 1 patient with ATRT) and 1 child with ependymoma in remission, as well as during chemotherapy. CT scans revealed multiple nodules of varying sizes within the heterogeneous adipose tissue of the abdominal cavity. MRI identified multiple solid isointense tumors on both T1- and T2-WI, exhibiting significant contrast enhancement and diffusion restriction. Tumor sizes ranged from 3 to 15 mm. A notable feature was the predominant spread in the interintestinal spaces, as well as the subdiaphragmatic and subhepatic regions, which complicates visualization. In one of the cases, imaging did not yield conclusive results, and metastases were confirmed only at autopsy.
Conclusion: Although shunt-associated metastasis in CNS tumors is extremely rare, it carries a very poor prognosis. Dynamic monitoring of children with brain tumor with a shunt system should include abdominal examinations (ultrasound or MRI). The development of an acute abdomen requires urgent evaluation to rule out tumor presence, including laparoscopy if indicated. Reports of such cases suggest that ventriculoperitoneal shunting for occlusive hydrocephalus should be considered only as a last resort when temporary external drainage is not feasible.
Limitations: N/A
Funding for this study: N/A
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: N/A

Author Block: M. L. Chia, K. Brindle; Cambridge/UK
Purpose: Given the poor therapy response noted in advanced stage High Grade Serous Ovarian Cancer (HGSOC) patients and the lack of fast and reliable treatment response monitoring methods, there is a need to predict treatment response earlier. This project investigated the potential of metabolic and cell death imaging techniques to detect early treatment response to standard-of-care chemotherapy in HGSOC patients.
Methods or Background: HGSOC cells, derived from the ascites of stage 3-4 HGSOC patients, were maintained as patient derived organoids(PDO) and implanted into mice subcutaneously. The resulting tumours were imaged with various imaging techniques. Metabolic imaging techniques included MRS (hyperpolarized [1-13C]pyruvate metabolism) and PET(measurements of 2-deoxy-2-[fluorine-18]fluoro-D-glucose uptake). Cell death imaging techniques included diffusion-weighted 1H MRI (DWI) and 2H MRSI measurements of [2,3-2H2]fumarate metabolism. PDO 2(carboplatin sensitive) and PDO 5(Carboplatin resistant) tumour models were treated with i.v. Carboplatin (50mg/kg) or drug vehicle weekly, with imaging at baseline and weekly thereafter.
Results or Findings: Both metabolic imaging techniques were successful in discriminating responding from non-responding tumours to Carboplatin before there was a change in tumour volume. The techniques for detecting cell death were not as sensitive for detecting treatment response, which may reflect a slow accumulation of dead cells post treatment, a lack of knowledge of when the rate of cell death increases post treatment and immune clearance of dead cells.
Conclusion: Imaging with hyperpolarized [1-13C]pyruvate has the potential to be used in the clinic to detect the early treatment response in HGSOC patients.
Limitations: We only tested Carboplatin but other chemotherapies or combination treatment regimens would also be important for investigation as they might produce a greater and faster increase in cell death, possibly allowing cell death detection techniques to be more successful. This will be part of future work.
Funding for this study: Cancer Research UK Cambridge Institute Core funding
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: Na