MRI Response Research Articles

Trigeminal nerve microstructure is linked with neuroinflammation and brainstem activity in migraine.

Although the pathophysiology of migraine involves a complex ensemble of peripheral and central nervous system changes that remain incompletely understood, the activation and sensitization of the trigeminovascular system is believed to play a major role. However, non-invasive, in vivo neuroimaging studies investigating the underlying neural mechanisms of trigeminal system abnormalities in human migraine patients are limited. Here, we studied 60 patients with migraine (55 females, mean age ± SD: 36.28 ± 11.95 years) and 20 age-/sex-matched healthy controls (19 females, mean age ± SD: 35.45 ± 13.30 years) using ultra-high field 7 Tesla diffusion tensor imaging and functional MRI, as well as PET with the translocator protein ligand [11C]-PBR28. We evaluated MRI diffusivity measures and PET signal at the trigeminal nerve root, as well as brainstem functional MRI response to innocuous, ophthalmic trigeminal nerve territory stimulation. Patients with migraine demonstrated altered white matter microstructure at the trigeminal nerve root (n=53), including reduced fractional anisotropy, compared to healthy controls (n=18). Furthermore, in patients, lower fractional anisotropy was accompanied by 1) higher neuroinflammation (i.e. elevated [11C]-PBR28 PET signal) at the nerve root (n=36) and 2) lower functional MRI activation in an ipsilateral pontine cluster consistent with spinal trigeminal nucleus (n=51). These findings were more robust on the right side, which was consistent with the observation that right headache dominant patients demonstrated higher migraine severity compared to left headache dominant patients in our cohort. Multimodal imaging of the integrated neural mechanisms that characterize migraine underscores the importance of trigeminal system remodeling as both a key aspect of the dynamics underlying migraine pathophysiology and a target for therapeutic interventions.

DOP119 Predicting response to anti-tumour necrosis factor-alpha therapy-α in fibrostenotic Crohn’s disease using infra-red microspectroscopy

Abstract Background Fibrostenotic strictures are common in Crohn’s disease, have limited treatment options and lack validated biomarkers to predict treatment response. Fourier-transform infra-red (FTIR) spectroscopy provides reproducible biochemical information from biospecimens using a rapid, label-free, non-destructive technique via molecular vibrations. We previously completed a proof-of-concept study that identified spectral biomarkers for inflammation in a model of colitis.1 The aim of this study was to investigate whether the tissue biochemical "fingerprint" using FTIR spectroscopy can predict patient clinical response to anti-tumour necrosis-factor-α (anti-TNFα) therapy, and identify spectral biomarkers for treatment response. Methods Hyperspectral images were acquired using the Agilent Cary 670 FPA-IR coupled with the Agilent Cary 620 microscope in transflection mode in the wavenumber region 1800 – 800 cm-1 from fixed ileo-colonoscopic biopsies from 62 patients with Crohn’s disease and 12 healthy controls. A subset of patients (n = 24) were included from STRIDENT2, a randomised study assessing adalimumab therapy for intestinal Crohn’s strictures. Thousands of spectra were obtained per sample, pre-processed via transformation to the second derivative, normalised and reduced to 25 spectra per sample prior to analysis using partial least squares discriminant analysis (PLSDA) with internal cross-validation. Spectral biomarkers were identified by the most contributive infra-red bands from the latent variables (LV) and significant variable importance in projection (VIP) scores of >1. Adjacent histological sections were stained with H&E, Masson’s trichrome and α-smooth muscle actin with inflammation and fibrosis scored by a clinical pathologist. Results Spectra from baseline biopsies from the 24 patients in the STRIDENT study demonstrated excellent performance using PLSDA in discriminating between responders and non-responders in relation to the 12 month clinical outcomes, defined by area under the receiver operating characteristic curve (AUC) >0.9 for MRI and IUS responses, normalisation of faecal calprotectin and CRP, CDAI and pain responses (Table 1). Spectral biomarkers of interest for stricture response to anti-TNFα are shown in Figure 1 and include the amide I and II protein bands (peaks at 1651 and 1543 cm-1, respectively), the carboxylate group of proteins (1454 cm-1), lipid bands (1750 and 1395 cm-1), collagen band (1236 cm-1), glycoprotein bands (1081 and 1030 cm-1), and nucleic acid bands (1236, 1081 and 966 cm-1). Conclusion The novel technique of FTIR spectroscopy detects tissue biochemical "fingerprints" in fibrostenotic Crohn’s disease that demonstrate excellent discrimination for predicting clinical response to adalimumab therapy.

Deep learning algorithms for predicting pathological complete response in MRI of rectal cancer patients undergoing neoadjuvant chemoradiotherapy: a systematic review

PurposeThis systematic review examines the utility of deep learning algorithms in predicting pathological complete response (pCR) in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT). The primary goal is to evaluate the performance of MRI-based artificial intelligence (AI) models and explore factors affecting their diagnostic accuracy.MethodsThe review followed PRISMA guidelines and is registered with PROSPERO (CRD42024628017). Literature searches were conducted in PubMed, Embase, and Cochrane Library using keywords such as “artificial intelligence,” “rectal cancer,” “MRI,” and “pathological complete response.” Articles involving deep learning models applied to MRI for predicting pCR were included, excluding non-MRI data and studies without AI applications. Data on study characteristics, MRI sequences, AI model details, and performance metrics were extracted. Quality assessment was performed using the PROBAST tool.ResultsOut of 512 initial records, 26 studies met the inclusion criteria. Most studies demonstrated promising diagnostic performance, with AUC values for external validation typically exceeding 0.8. The use of T2W and diffusion-weighted imaging (DWI) MRI phases enhanced model accuracy compared to T2W alone. Larger datasets generally correlated with improved model performance. However, heterogeneity in model designs, MRI protocols, and the limited integration of clinical data were noted as challenges.ConclusionAI-enhanced MRI demonstrates significant potential in predicting pCR in rectal cancer, particularly with T2W + DWI sequences and larger datasets. While integrating clinical data remains controversial, standardizing methodologies and expanding datasets will further enhance model robustness and clinical utility.

Magnetic chromatography improves colloidal and MRI attributes of magnetoliposomes enabling evaluation of the impact of size on bio-distribution in an in vivo model of pancreatic cancer.

Magnetic chromatography was exploited to fractionate suspensions of magnetoliposomes (SML: lumen-free lipid-encapsulated clusters of multiple magnetic iron-oxide nanoparticles) improving their colloidal properties and relaxivity (magnetic resonance image contrast capability). Fractionation (i) removed sub-populations that do not contribute to the MRI response, and thus (ii) enabled evaluation of the size-dependence of relaxivity for the MRI-active part, which was surprisingly weak in the 55-90 nm range. MC was therefore implemented for processing multiple PEGylated SML types having average sizes ranging from 85 to 105 nm, which were then shown to have strongly size-dependent uptake in an in vivo pancreatic cancer model. Hence for applications in cancer diagnosis, selection of SML of suitable size for the biological target is more important than size-dependence of relaxivity.

Human Papilloma Virus Circulating Cell-Free DNA Kinetics in Cervical Cancer Patients Undergoing Definitive Chemoradiation.

The human papillomavirus (HPV) is a significant cause of cervical cancer. We hypothesized that detecting viral cell-free HPV DNA (cfDNA) before, during, and after chemoradiation (chemoRT) could provide insights into disease extent, clinical staging, and treatment response. Sixty-six patients with locally advanced cervical cancer were enrolled between 2017 and 2023. 49 received standard-of-care (SOC) treatment and 17 participated in a clinical trial combining a therapeutic HPV vaccine (PDS0101; IMMUNOCERV). Plasma was collected at baseline, weeks 1, 3, and 5 of chemoRT, and 3-4 months after chemoRT. HPV cfDNA was quantified using droplet digital PCR targeting the HPV E6/E7 oncogenes of 13 high-risk types. MRI was performed at baseline and before brachytherapy. The median follow-up was 23 months, with recurrence-free survival (RFS) of 78.4% at 2 years. Baseline nodal disease extent correlated with HPV cfDNA levels. HPV cfDNA levels peaked in week 1 of radiation and decreased through treatment. Patients receiving the PDS0101 vaccine had a higher rate of undetectable HPV type 16 cfDNA compared to SOC. HPV cfDNA clearance correlated with better 2-yr RFS (92.9% vs. 30%, log-rank p=0.0067). The strongest predictor of RFS was HPV cfDNA clearance in follow-up achieving a concordance index (CI) 0.83, which improved when combined with MRI response (CI 0.88). HPV cfDNA levels change dynamically during chemoRT. HPV cfDNA at follow-up predicts RFS. Delivery of therapeutic HPV vaccine with chemoRT was linked to rapid HPV cfDNA decline. Monitoring HPV cfDNA during and after chemoRT may guide tailoring of personalized treatment.

Development and Evaluation of Automated Artificial Intelligence-Based Brain Tumor Response Assessment in Patients with Glioblastoma.

To develop and evaluate an automated, AI-based, volumetric brain tumor MRI response assessment algorithm on a large cohort of patients treated at a high-volume brain tumor center. We retrospectively analyzed data from 634 patients treated for glioblastoma at a single brain tumor center over a 5-year period (2017-2021). The mean age was 56 +/-13 years. 372/634 (59%) patients were male, and 262/634 (41%) patients were female. Study data consisted of 3,403 brain MRI exams and corresponding standardized, radiologist-based brain tumor response assessments (BT-RADS). An artificial intelligence (AI)-based brain tumor response assessment algorithm was developed using automated, volumetric tumor segmentation. AI-based response assessments were evaluated for agreement with radiologist-based response assessments and ability to stratify patients by overall survival. Metrics were computed to assess the agreement using BTRADS as the ground-truth, fixed-time point survival analysis was conducted to evaluate the survival stratification, and associated P-values were calculated. For all BT-RADS categories, AI-based response assessments showed moderate agreement with radiologists' response assessments (F1 = 0.587-0.755). Kaplan-Meier survival analysis revealed statistically worse overall fixed time point survival for patients assessed as image worsening equivalent to RANO progression by human alone compared to by AI alone (log-rank P=0.007). Cox proportional hazard model analysis showed a disadvantage to AI-based assessments for overall survival prediction (P=0.012). AI-based volumetric glioblastoma MRI response assessment following BT-RADS criteria yielded moderate agreement for replicating human response assessments and slightly worse stratification by overall survival. GBM＝ Glioblastoma; RANO＝ Response Assessment in Neuro-Oncology; BTRADS＝ Brain Tumor Reporting and Data System; NLP = Natural Language Processing.

RADT-50. CLINICAL OUTCOME OF DAILY 5-FRACTIONATED GAMMA KNIFE RADIOSURGERY FOR LARGE BRAIN METASTASES

Abstract INTRODUCTION With the introduction of the Gamma Knife Icon, hypo-fractionated Gamma Knife radiosurgery (GKRS) for large brain metastases (LBMs) is beginning to be performed. This study aimed to assess the clinical outcome and risk of the daily 5-fractionated GKRS for LBMs. METHODS A total of 100 patients who underwent 5-fractionated GKRS for LBMs (> 14cm3) were enrolled. Forty-six were male patients, and the median age was 60 years. Most common primary cancer sites were lung (41 non-small cell cancers), breast (24), and kidney (14). The median tumor volume was 22cm3 (14 – 69cm3) and marginal dose was 35Gy (50% isodose line) in 5 fractions. Median follow-up duration was 18 months (3 – 72 months). RESULTS The last follow-up showed local tumor control in 74 cases. The cumulative 1, 2, and 3-year local tumor control rates were 73, 65, and 60%, respectively. Eighty-six tumors showed best MRI response in a year, and median tumor volume decrease rate was 80% (22 – 100%). Thirty patients experienced dramatically tumor volume decrease (> 95%). Median progression free and overall survival were 7 and 16 months, respectively. Radiation necrosis occurred in 24 patients, of which only 9 had neurological symptoms and treated with steroid and bevacizumab. CONCLUSIONS The daily 5-fractionated GKRS for very LBMs showed favorable local tumor control and acceptable radiation necrosis, but questionable survival benefit. In the future, prospective multi-center study is needed.

NIMG-16. ASSESSMENT OF RESPONSE TO LOMUSTINE-TEMOZOLOMIDE CHEMOTHERAPY IN ADDITION TO RADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA USING FET PET

Abstract BACKGROUND We examined the value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for early response assessment in patients with newly diagnosed glioblastoma and methylated O6-methylguanine-DNA methyltransferase promoter treated with lomustine-temozolomide chemotherapy in addition to radiotherapy. METHODS Thirty-one patients (29-74 years) were treated according to the CeTeG/NOA-09 phase-3 trial. FET PET and anatomical MRI were performed at baseline and follow-up after the third cycle. We obtained mean and maximum tumor-to-brain ratios (TBR) and metabolic tumor volumes (MTV). Thresholds derived from FET PET were defined using receiver operating characteristic analyses to predict progression-free survival (PFS) of ≥12 months. The predictive value of FET PET parameters was subsequently evaluated using univariate and multivariate survival estimates. MRI response assessment was based on the RANO 1.0 criteria. FET PET data were also used to estimate response according to the PET RANO 1.0 criteria. RESULTS Patients received a median number of 6 cycles of lomustine-temozolomide chemotherapy (3-6 cycles). After treatment initiation, the median follow-up was 17.2 months (7.2-59.4 months). As of April 2024, we confirmed tumor progression according to the RANO 1.0 criteria in 24 patients (77%). After three cycles of lomustine-temozolomide chemotherapy, a reduced mean TBR value by ≥10% predicted a significantly longer PFS (31.0 vs. 10.4 months; P=0.039). In contrast, changes in maximum TBR values, MTV, the RANO 1.0 criteria, and the PET RANO 1.0 criteria were not predictive for response (P>0.05). Multivariate survival analysis revealed that changes in mean TBR values predicted a significantly prolonged PFS independent of age, the extent of resection, and the Karnofsky Performance Status (P=0.036; HR, 3.892; 95% CI, 1.242-17.230). CONCLUSION Our results suggest that FET PET is clinically valuable for identifying responders to lomustine-temozolomide chemotherapy in addition to radiotherapy early after treatment initiation. The evaluation of FET PET’s value in predicting a significantly longer overall survival is ongoing.

Dynamics of cell-free tumor DNA correlate with early MRI response during chemoradiotherapy in rectal cancer

BackgroundIn locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification.MethodsIn 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters.ResultsMost patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5.ConclusionsWeekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found.

Analysis of Adherence to AAO-HNSF Clinical Practice Guidelines for Sudden Hearing Loss.

To assess adherence to the 2019 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNSF) guidelines for the diagnosis and management of sudden hearing loss (SHL) and sudden sensorineural hearing loss (SSNHL). Retrospective cohort. TriNetX, a de-identified healthcare database. Evaluation focused on the percentage of patients undergoing proper guideline-adherent workup and treatment for SHL. Key measures include audiogram testing within 2 weeks for distinguishing SSNHL from CHL. For SSNHL patients, MRI or auditory brainstem response (ABR) testing should be obtained, and steroids and/or hyperbaric oxygen may be offered within 2 weeks. There were 24,203 SHL patients, 59.1% (n = 14,309) of whom underwent recommended audiogram testing, with 35.8% (n = 8,674) completing it within 2 weeks. Overall, 3,107 were diagnosed with unilateral SSNHL, 104 with unilateral conductive hearing loss (CHL), 121 with mixed hearing loss, and 10,977 were lost to follow-up. Among 3,107 SSNHL cases, just 25.5% (n = 791) obtained MRI/ABR within 1 month, and vestibular schwannoma was diagnosed in 3.5% (n = 28). Additionally, steroids were prescribed to 54.5% (n = 1,692), and <0.3% (n ≤ 10) received hyperbaric oxygen. In accordance with strong recommendations against or insufficient evidence to support the following diagnostics and treatments, 2.0% (n = 63) underwent a CT scan, less than 0.3% (n ≤ 10) were prescribed vasodilators or thrombolytics, and 3.5% (n = 108) were on antivirals. There is a significant opportunity for improvement in evaluating patients with SHL, specifically SSNHL. Proper adherence to guidelines may improve screening, detection, and management of neurotologic pathologies, including vestibular schwannoma.

Neural correlates of systemic lidocaine administration in healthy adults measured by functional MRI: a single arm open label study.

Intravenous lidocaine is increasingly used as a nonopioid analgesic, but how it acts in the brain is incompletely understood. We conducted a functional MRI study of pain response, resting connectivity, and cognitive task performance in volunteers to elucidate the effects of lidocaine at the brain-systems level. We enrolled 27 adults (age 22-55 yr) in this single-arm, open-label study. Pain response task and resting-state functional MRI scans at 3 T were obtained at baseline and then with a constant effect-site concentration of lidocaine. Electric nerve stimulation, titrated in advance to 7/10 intensity, was used for the pain task (five times every 10 s). Group-level differences in pain task-evoked responses (primary outcome, focused on the insula) and in resting connectivity were compared between baseline and lidocaine conditions, using adjusted P<0.05 to account for multiple comparisons. Pain ratings and performance on a brief battery of computer-based tasks were also recorded. Lidocaine infusion was associated with decreased pain-evoked responses in the insula (left: Z=3.6, P<0.001, right: Z=3.6, P=0.004) and other brain areas including the cingulate gyrus, thalamus, and primary sensory cortex. Resting-state connectivity showed significant diffuse reductions in both region-to-region and global connectivity measures with lidocaine. Small decreases in pain intensity and unpleasantness and worse memory performance were also seen with lidocaine. Lidocaine was associated with broad reductions in functional MRI response to acute pain and modulated whole-brain functional connectivity, predominantly decreasing long-range connectivity. This was accompanied by small but significant decreases in pain perception and memory performance. NCT05501600.

Tumor response rates based on initial TNM stage and tumor size in locally advanced rectal cancer: a useful tool for shared decision-making.

It is accepted that tumor stage and size can influence response to neoadjuvant therapy in locally advanced rectal cancer (LARC). Studies on organ preservation to date have included a wide variety of size and TNM stage tumors. The aim of this study was to report tumor response based on each relevant TNM stage and tumor size. Patients treated with LARC from 2014 to 2021 with cT2-3NxM0 tumors who received neoadjuvant chemoradiotherapy with or without induction chemotherapy were included. Tumors were staged and tumor size calculated on pelvic MRI at the time of diagnosis (cTNM). Tumor size was based on the largest dimension taken on the longest axis of each tumor. Clinical response was defined on the basis of post-treatment pelvic MRI and pathological response following surgery, when performed. Statistical analysis was performed using IBM SPSS Statistics™, version20. Data from 432 patients were analyzed as follows: cT2N0 (n = 51), cT2N+ (n = 36), cT3N0 (n = 76), cT3N+ (n = 270). The rate of complete or near-complete response (cCR or nCR) varied from 77% in cT2N0 ≤ 3cm to 20% in cT3N+ > 4cm. Organ preservation without recurrence at 2years was achieved in 86% of patients with cT2N0, 50% in cT2N+, 39% in cT3N0, and 12% in cT3N+. There is significant variation in tumor response according to tumor stage and size. Tumor response appears inversely proportional to increasing TNM stage and tumor size. This data can support both refinement of selective patient recruitment to organ preservation programs and shared decision-making.

MRI Predicts Residual Disease and Outcomes in Watch-and-Wait Patients with Rectal Cancer.

Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT. Participants enrolled in the OPRA trial who underwent restaging MRI were eligible for inclusion in the present study. Radiologists classified participants as having clinical complete response (cCR), near-complete clinical response (nCR), or incomplete clinical response (iCR) based on restaging MRI at a mean of 8 weeks ± 4 (SD) after treatment. Oncologic outcomes according to MRI response category were assessed using Kaplan-Meier curves. Logistic regression analysis was performed to identify imaging characteristics associated with RD. Results A total of 277 participants (median age, 58 years [IQR, 17 years]; 179 male) who were randomized in the OPRA trial had restaging MRI forms completed. The median follow-up duration was 4.1 years. Participants with cCR had higher rates of organ preservation compared with those with nCR (65.3% vs 41.6%, log-rank P < .001). Five-year disease-free survival for participants with cCR, nCR, and iCR was 81.8%, 67.6%, and 49.6%, respectively (log-rank P < .001). The MRI response category also predicted overall survival (log-rank P < .001), distant recurrence-free survival (log-rank P = .005), and local regrowth (log-rank P = .02). Among the 266 participants with at least 2 years of follow-up, 129 (48.5%) had RD. At multivariable analysis, the presence of restricted diffusion (odds ratio, 2.50; 95% CI: 1.22, 5.24) and abnormal nodal morphologic features (odds ratio, 5.04; 95% CI: 1.43, 23.9) remained independently associated with RD. Conclusion The MRI response category was predictive of organ preservation and survival. Restricted diffusion and abnormal nodal morphologic features on restaging MRI scans were associated with increased likelihood of residual tumor. ClinicalTrials.gov identifier: NCT02008656 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Milot in this issue.

Arterial Mucosal Linear Enhancement at Contrast-enhanced MRI to Exclude Residual Tumor after Neoadjuvant Chemotherapy and Radiation Therapy for Rectal Cancer.

Background A watch-and-wait regimen for locally advanced rectal cancer after neoadjuvant chemotherapy and radiation therapy (NCRT) relies on identifying complete tumor response. However, the concordance between a complete response at combined T2-weighted and diffusion-weighted MRI (T2DWI) and pathologic complete response (pCR; ie, ypT0N0) in the tumor is unsatisfactory. Purpose To assess whether identification of mucosal linear enhancement (MLE) at arterial-phase contrast-enhanced (CE) T1-weighted MRI is associated with ypT0 status in patients with locally advanced rectal cancer after NCRT and to evaluate whether combining MLE at CE T1-weighted MRI and negative lymph node metastasis (LNM) at T2DWI can improve identification of pCR. Materials and Methods This retrospective study included patients with locally advanced rectal cancer who underwent total mesorectal excision after NCRT between July 2020 and July 2023 at a tertiary referral academic center. Restaging MRI included T2DWI and arterial-phase CE T1-weighted MRI for primary tumor assessment and T2DWI for evaluation of LNM status. Imaging features associated with ypT0 status were identified at multivariable regression analysis. Results In total, 239 patients (mean age, 58 years ± 12 [SD]; 180 male patients) were assessed. MLE was more common in the ypT0 group than in the ypT1-4 group after NCRT (73% vs 4%, respectively; P < .001). MLE was associated with higher odds of ypT0 status in an adjusted analysis (odds ratio, 137; 95% CI: 25, 767; P < .001). The combination of MLE and negative LNM status achieved an area under the receiver operating characteristic curve of 0.84 (95% CI: 0.79, 0.88) for pCR. Conclusion MLE at CE MRI was associated with higher odds of complete tumor response. Combining MLE and negative LNM status showed good performance for identifying complete tumor response and may exclude residual tumors after NCRT in patients with locally advanced rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Schoellnast in this issue.

MOG Antibody-Associated Disease in the Setting of Metastatic Melanoma Complicated by Immune Checkpoint Inhibitor Use.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disease rarely associated with malignancy. We report the clinical, MRI, immunopathology, and treatment response in a person with MOGAD and melanoma. This is a case report of a person with a multidisciplinary evaluation at a tertiary referral center. A 52-year-old man presented with progressive encephalomyelitis that led to identification of metastatic melanoma. Investigations revealed positive MOG-IgG at high titers in serum (1:1,000; normal, <1:20) and CSF (1:4,096; normal, <1:2). MRI demonstrated multifocal T2 lesions with enhancement in the brain and spine. Brain biopsy showed demyelination and inflammation. MOG immunostaining was not present in the tumor tissue. He initially improved with methylprednisolone, plasmapheresis, prolonged oral steroid taper, and cancer-directed treatment with BRAF and MEK 1/2 inhibitors, but then developed bilateral optic neuritis. IV immunoglobulin (IVIG) was initiated. Five months later, he developed metastases and immune checkpoint inhibitor (ICI) treatment was started, which precipitated optic neuritis and myelitis despite IVIG and prednisone. Tocilizumab, an interleukin-6 receptor blocker, was started with excellent and sustained clinical and radiologic response. This case revealed a presentation of MOGAD concurrent with melanoma without tumor MOG immunostaining. We highlight tocilizumab as a dual-purpose treatment of MOGAD and the neurologic immune-related adverse effect of ICI.

Primary central nervous system lymphomas in immunocompromised patients require specific response criteria.

Immunosuppression is a well-established risk factor for primary central nervous system lymphomas (PCNSLs), which present in this context distinct radiological characteristics. Our aim was to describe the radiological evolution of treated PCNSL in immunocompromised patients and suggest adapted MRI response criteria. We conducted a multicenter retrospective study of patients from the French LOC, K-Virogref and CANCERVIH network databases and enrolled adult immunocompromised patients with newly diagnosed PCNSL. We evaluated the baseline, intermediate, end-of-treatment and follow-up MRI data of 31 patients (9 living with HIV, 16 with solid organ transplantation and 6 with an autoimmune disease under chronic immunosuppressive therapy). At baseline, 23/30 (77%) patients had necrotic lesions with ring enhancement and 28% of the lesions were hemorrhagic. At the end of the first-line treatment, 12/28 (43%) patients could not be classified according to the IPCG criteria. Thirteen of 28 (46%) patients still harbored contrast enhancement, and 11/28 (39%) patients had persistent large necrotic lesions with a median diameter of 15mm. These aspects were not associated with a pejorative outcome and progressively diminished during follow-up. Six patients relapsed; however, we failed to identify any neuroimaging risk factors on the end-of-treatment MRI. In immunocompromised patients, PCNSLs often harbor alarming features on end-of-treatment MRI, with persistent contrast-enhanced lesions frequently observed. However, these aspects seemed to be related to the necrotic and hemorrhagic nature of the lesions and were not predictive of a pejorative outcome. Specific response criteria for this population are thereby proposed.

NeoTRACT: Phase II trial of neoadjuvant tumor infiltrating lymphocyte- and response-adapted chemoimmunotherapy for triple-negative breast cancer (TNBC).

TPS629 Background: Neoadjuvant chemoimmunotherapy is recommended for patients with high risk early stage TNBC. The 5 drug KEYNOTE-522 neoadjuvant chemoimmunotherapy regimen involves 5-6 months of treatment and is associated with suboptimal treatment completion due to toxicity. Approaches to deescalate chemoimmunotherapy without compromising outcomes for patients with highly chemosensitive disease are needed. Stromal tumor infiltrating lymphocyte (sTIL) enrichment is positively associated with pathologic complete response (pCR) in TNBC and may be useful to identify patients for whom de-escalation of neoadjuvant chemoimmunotherapy might be acceptable. NeoTRACT trial investigates deescalating neoadjuvant chemoimmunotherapy based on degree of pretreatment sTIL enrichment. We hypothesize that baseline immune upregulation assessed by sTILs can guide neoadjuvant treatment optimization in TNBC patients. Specifically, in patients with immune enriched TNBC (sTILs ≥30%), short anthracycline free taxane–platinum chemoimmunotherapy will yield high pCR rate. Methods: NeoTRACT is an ongoing open label phase II trial for patients with previously untreated TNM stage I (T&gt;1cm)–III TNBC. TNBC is defined as estrogen and progesterone receptor ≤10% and HER2 negative per ASCO/CAP criteria. Patients with T4 or N3 breast cancer are excluded. Patients must have adequate organ function and no contraindication to pembrolizumab. All participants initiate carboplatin (AUC 6) + docetaxel (75mg/m2) + pembrolizumab (200mg) (CbD+P) every 21 days. After registration, sTILs are evaluated centrally on pretreatment H&amp;E core needle biopsy slide using standard criteria. Participants are assigned to three neoadjuvant treatment regimens (A, B, or C) based on sTIL enrichment. Regimen A (sTILs ≥30%) includes four cycles CbD+P. All participants assigned to regimen A undergo breast MRI after four cycles: those with complete MRI response proceed to breast surgery; those with less than complete MRI response receive two additional cycles of CbD+P. Regimen B (sTILs 5-29%) includes six cycles of CbD+P. Regimen C (sTILs &lt;5%) includes four cycles of CbD+P followed by four cycles of doxorubicin (60mg/m2) + cyclophosphamide (600mg/m2) + P (200mg) (AC+P). All patients undergo surgery after completing the assigned neoadjuvant regimen. Breast/axillary surgery, adjuvant systemic therapy, and radiotherapy are recommended per standard of care. pCR is defined as absence of residual invasive disease in breast and axilla. Primary endpoint is pCR rate among participants with ≥30% sTILs. Secondary endpoints include residual cancer burden (RCB) rates in patients with ≥30% sTILs, pCR and RCB rates in patients with 5-29% and &lt;5% sTILs, and event free and overall survival for all patients. As of January 2024, 45 of 139 participants have been enrolled. Clinical trial information: NCT05645380 .

Abstract PO3-07-06: Correlation between residual microcalcification and in-breast pathologic response in relation to MRI response and the subtypes after neoadjuvant chemotherapy

Abstract Background The significance of residual microcalcifications after neoadjuvant chemotherapy (NAC) in determining the extent of surgical intervention in breast cancer remains unclear. This study aimed to assess whether residual microcalcifications after NAC correlate with the residual disease in patients with breast cancer stratified by subtypes, particularly in excellent radiologic responders. Methods We conducted a retrospective study of patients with breast cancer who underwent NAC followed by curative surgery between January 2007 and December 2022. We evaluated the presence of suspicious microcalcifications on pre-NAC mammography and residual microcalcifications on post-NAC mammography. In the patients who had residual microcalcifications on post-NAC mammography, the rates of breast pathologic complete response (pCR), defined as the absence of invasive cancer (ypT0/is) or complete breast pCR defined as the absence of invasive cancer and in-situ cancer in the breast (ypT0), was assessed according to the MRI response and subtypes. We defined complete MRI response as the resolution of suspicious enhancement in the breast and axilla after NAC. Results Of the 1078 patients, 554 (51.4%) had suspicious microcalcifications at baseline, of which 518 (93.5%) had residual microcalcifications after NAC. Among the 518 patients with residual microcalcifications, 93 (18.0%) achieved a complete MRI response. We observed a difference in breast pCR rates depending on MRI response and hormone-receptor (HR) status. In the patients without complete MRI response, about one-third of patients (139 of 425 [32.7%]) achieved a breast pCR, irrespective of HR status (19.3% [47 of 244] in HR-positive breast cancer and 50.8% [92 of 181] in HR- negative breast cancer). Of the 93 patients who achieved a complete MRI response, the breast pCR rates were 64.3% (27 of 42) in HR-positive breast cancer and 96.1% (49 of 51) in HR-negative breast cancer, respectively. Moreover, the breast complete pCR rate was 54.8% (23 of 51) in HR-positive breast cancer and 88.2% (45 of 51) in HR-negative breast cancer, including 87.2% (34 of 39) in HR-HER2+ breast cancer and 91.7% (11 of 12) in triple-negative breast cancer. Conclusion Our results suggest that the clinical relevance of the residual microcalcifications differs according to the breast cancer subtypes. For patients with HR-positive breast cancer, removal of the residual microcalcifications should be considered to ensure complete cancer removal, regardless of MRI response. In contrast, de-escalating surgery may be considered in patients with HR-negative breast cancer who achieve complete MRI response after NAC. Citation Format: Soong June Bae, Seung Ho Baek, Seung Eun Lee, Min Ji Kim, Sohyun Moon, Junghyun Kim, Yoonwon Kook, Joon Jeong, Sung Gwe Ahn. Correlation between residual microcalcification and in-breast pathologic response in relation to MRI response and the subtypes after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-07-06.

Abstract PO2-22-06: MRI response Assessment of Single Fraction Pre-operative Stereotactic Radiotherapy: Preliminary results

Abstract Background: Pre-operative stereotactic breast irradiation (SPBI) improves targeting precision and has the potential to decrease treatment-related toxicity while downstaging or eliminating cancer. Accurate pCR prediction may allow omission of surgery. We are reporting initial interim results of the performance of multiparametric breast MRI in identifying pathologic response rate after single-fraction pre-operative SPBI in early stage estrogen receptor-positive (ER+), HER-2 negative breast cancer. Methods: In an ongoing single center prospective single-arm trial 22 patients with ER+/HER2-negative, cN0, unifocal, invasive breast cancer ≤3 cm underwent single-dose ablative SPBI, followed by definitive surgery per standard of care. Residual disease vs complete imaging response to SPBI was assessed on baseline and post-SPBI/pre-operative breast MRI. Pathologic response was categorized using MDACC Residual Cancer Burden (RCB) Categories. Wilcoxon rank sum test was used to assess the correlation of pathologic complete response (pCR) or RCB status on final path with MRI lesion size, volume, diffusion weighted imaging apparent diffusion coefficient (ADC) value, and when available, presence of residual enhancement on pre-operative MRI. MRI volume and ADC values were obtained using a dedicated CAD software. Area under the receiver operating Curve(AUC) was constructed to assess the diagnostic performance of pre-operative MRI on predicting pathologic response. Results Mean patient age was 64.9 (SD±7.3) years, tumor diameter 1.2(± 0.6) cm, pre-SPBI volume 6.4 ± 9.1 cm3, post SPBI volume 1.8 ± 5.6 cm3, ADC 0.91 ×10-3 mm2/s. At surgical pathology, 6(27.2%) achieved pCR/RCB-0, 9(41%) RCB-I, 7(31.8%) RCB-II. Mean baseline MRI size (1.2 ± 0.7 vs 1.3 ± 0.6, p=0.88), enhancement volumes (6.0±6.2 vs 7.9±9.9 cm3, p=0.59), DWI ADC values (1.1 ± 0.3 vs 0.9 ± 0.2 mm2/s, p-0.48) were not significantly different between tumors that showed pCR vs RCB I-II at surgical pathology. Time elapsed from SBRT to surgery were significantly longer in patients with pCR (264.3 ± 74.2 vs 183.7 ± 68.3 days, p=0.04) On pre-op MRI, mean enhancement volume was smaller in cancers that had pCR, however it did not reach significance (0.1 ± 0.1 vs 2.1 ± 6.0 cm3, p=0.2). Of 18 patients with available pre-operative MRI, residual enhancement was present in 7, of these 6/7(87%) had RCB I-II, and 1/7(13%) RCB-0 at surgical pathology. Conversely, in 11 patients with no residual enhancement on MRI, pathology showed pCR/RCB-0 in 5(45.5%), while 6(54.5%) had RCB I or II. Presence of residual enhancement on pre-operative MRI had an AUC of 0.68 (95%CI 0.43; 0.93, p=0.2) in predicting residual cancer after SPBI. Conclusion: Detecting residual enhancement on pre-operative MRI is a strong indicator of residual disease after SPBI, while lack of enhancement is not a reliable predictor of pCR. Our preliminary results do not indicate an association between baseline MRI enhancement volume, DWI ADC and pathologic response. Citation Format: Baṣak Dogan, Sunati Sahoo, Marilyn Leitch, Prasanna Alluri, Robert Timmerman, Deborah Farr, Asal Rahimi. MRI response Assessment of Single Fraction Pre-operative Stereotactic Radiotherapy: Preliminary results [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-06.

Abstract PO2-23-04: Magnetic Seeds, used to Locate the Metastatic Axillary Lymph Node placed before Neoadjuvant Chemotherapy for Breast Cancer Treatment, do not interfere the pre-surgical MRI Breast response assessment

Abstract Background: Axillary management in clinically node-positive patients who converted to ycN0 after neoadjuvant chemotherapy (NAC) for breast cancer (BC) remains under research with the aim of de-escalation of axillary lymph node dissection (ALND). A magnetic seed is one of the several positive lymph nodes marking techniques used in targeted axillary dissection (TAD) for patients with cN1 breast cancer undergoing neoadjuvant systemic therapy. It has been criticized for its potential masking effect due to the artefact it produces in the MRI sequences used to assess a proper breast response. This study evaluates if the magnetic seeds placed before NAC for guided TAD have influenced in the breast MRI response assessments. Methods: From October 2021 to June 2023, patients with cT0-4 cN1 breast cancer who were candidates for primary systemic treatment were prospectively recruited. Once a breast lesion and axillary node positivity were confirmed, a based hydrogel marker and a magnetic seed, respectively, were placed prior NAC. Once systemic treatment was completed, imaging techniques were used to assess the response, with MRI being the imaging technique of choice to assess breast response and axillary ultrasound the imaging technique of choice to assess axillary response. Surgical pathological confirmation of response in the axilla was by TAD, including sentinel lymph node and magnetic clipped node resection. Results: A total of 43 patients were included and their characteristics are shown in Table 1. In 16 patients (37%) the tumour was located in the upper outer quadrant (UOQ). In this group, the susceptibility artefact produced by the magnetic seed in the MRI created a black hole obscuring the axilla with a mean diameter of 69 mm (range: 57-76 mm). In no case did the halo interfere with the correct MRI visualisation of the breast marker. By MRI, the mean distance of the artifact halo from the breast marker or residual breast lesion was 40 mm (range: 13-79 mm). Overall, complete radiological response (ycCR) was reported in 20 patients (46%), breast only in 21 (49%) and axilla only in 38 (88%) patients. In 5 patients, preoperative axillary ultrasound revealed residual axillary disease, confirmed by FNA, lead to direct ALND. In the remaining 38 patients the axillary TAD assessment was completed. In all cases, the magnetic clipped node was successfully surgically removed. Pathological complete response (pCR) was confirmed in 9 (21%), breast only in 11 (26%) and axilla only in 13 (30%) patients. MRI diagnostic performance in detecting residual breast disease after NAC was not altered by the magnetic clipped node artifact when comparing the tumour location in the UOQ to the other quadrants (AUC 0.764 vs. 0.702; p=0.698). Conclusions: Surgical axillary staging remains the most reliable method for assessing the axillary response after NAC. Target axillary dissection guided by magnetic seed placed before NAC is an effective and accurate technique. The artifact generated in the MRI does not interfere with the pre-surgical breast response assessment after neoadjuvant systemic treatment. Table 1: Patients and tumor characteristics Citation Format: Martin Espinosa-Bravo, Joaquin Rivero Deniz, Clara Morales Comas, Javier de la Torre Fernandez de Vega, Irene Vives Rosello, Enrica Esposito, Vicente Peg Camara, María De Les Neus Rus Calafell, Ignacio Miranda Gomez, Christian Siso Raber. Magnetic Seeds, used to Locate the Metastatic Axillary Lymph Node placed before Neoadjuvant Chemotherapy for Breast Cancer Treatment, do not interfere the pre-surgical MRI Breast response assessment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-04.