Post-treatment Magnetic Resonance Imaging Research Articles

Diffusion Weighted and Dynamic Contrast Enhanced Magnetic Resonance Imaging in Carcinoma of Cervix: Role of Apparent Diffusion Coefficient Value and Time Intensity Curve Pattern in Chemoradiotherapeutic Response Evaluation

Introduction: Magnetic resonance imaging (MRI) is a widely used imaging modality in the imaging evaluation of carcinoma of cervix. The aim of our study was to evaluate the response in carcinoma cervix patients following chemoradiotherapy by Diffusion weighted (DW-MRI) and Dynamic contrast enhanced-MRI (DCE-MRI). Methods: 21 inoperable biopsy proven patients (mean age 48.43 years) of carcinoma cervix were included in the study. All patients underwent MRI (conventional, DW and DCE) of the pelvis thrice. Baseline MRI, Post chemotherapy MRI after neoadjuvant chemotherapy and Post chemoradiotherapy MRI after completion of concurrent chemoradiotherapy. Post treatment apparent diffusion coefficient(ADC) values and Time intensity curve(TIC) pattern were compared with baseline values. Results: Baseline meanADC value of all patients was 0.82 x10-3 mm2/s. After completion of treatment, 18 patients showed complete resolution of tumor and showed 0.50 x10-3 mm2/s increase in meanADC value from baseline MRI which was significantly higher than remaining 3 patients with residual tumor (0.50 x10-3 mm2/s v/s 0.17 x10-3 mm2/s). ADC threshold value of 1.15 x10-3 mm2/s was defined, differentiating the residual tumor from the healthy cervical tissue after chemoradiation. On post treatment MRI, 17 out of 18 patients with complete resolution of tumor showed increasing trend of enhancement on TIC and only one patient showed plateau pattern. 2 of the 3 patients with residual tumor showed washout pattern and one patient showed plateau pattern. Conclusion: ADC values and TIC pattern differ in patients with complete response to chemoradiotherapy from patients with residual tumor, so helps in differentiating residual tumor from cancer free cervix. Keywords: Carcinoma of cervix; Chemoradiotherapy; Diffusion weighted MRI; Dynamic contrast enhanced MRI; Time intensity curve.

Image Guided Injection of Anterior Cruciate Ligament Tears with Autologous Bone Marrow Concentrate and Platelets: Midterm Analysis from A Randomized Controlled Trial

Background: There has been a recent emergence in the use of orthobiologics, including platelet-rich plasma (PRP) and bone marrow concentrate (BMC), in the treatment of various musculoskeletal conditions. The goal of this study was to determine if injection of BMC and platelet products into partial and full-thickness anterior cruciate ligament (ACL) tears can facilitate primary ligament healing in patients failing conservative care, resulting in improved outcomes compared to exercise therapy.Methods: Patients were randomized to either exercise therapy or percutaneous injection of autologous BMC with PRP and platelet lysate into the ACL under fluoroscopic guidance. Pain and function were assessed at baseline and at 1, 3, 6, 12, and 24 months. Baseline and 6-month post-treatment magnetic resonance imaging (MRI) were obtained to evaluate interval healing. Laxity was assessed using the Telos device.Results: There was significant improvement in functional outcomes in the BMC group, compared to base-line for LEFS at time points 3 up to 24 months s = 0.000000005), and significant improvement in pain in the BMC group at 6 (p = 0.00054), 12 (p = 0.00127), and 24 months (p = 0.002). There was no significant improvement in pain or function at any time point in the exercise therapy group. There was significant improvement in ACL MRI ImageJ quantitative assessment in the BMC group (p = 0.001) and no difference in the exercise group (p > 0.05). No serious adverse events were reported.Conclusion: Autologous BMC and platelet product injection into ACL tears improved patient function compared to exercise, observed through 24 months. Patients treated with BMC demonstrated quantitative improvements in post-treatment MRI scans suggestive of interval ligament healing.

Magnetic Resonance Imaging in the Contemporary Management of Medulloblastoma: Current and Emerging Applications.

Medulloblastoma, the most common malignant primary brain tumor in children, is now considered to comprise of four distinct molecular subgroups-wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4 medulloblastoma, each associated with distinct developmental origins, unique transcriptional profiles, diverse phenotypes, and variable clinical behavior. Due to its exquisite anatomic resolution, multiparametric nature, and ability to image the entire craniospinal axis, magnetic resonance imaging (MRI) is the preferred and recommended first-line imaging modality for suspected brain tumors including medulloblastoma. Preoperative MRI can reliably differentiate medulloblastoma from other common childhood posterior fossa masses such as ependymoma, pilocytic astrocytoma, and brainstem glioma. On T1-weighted images, medulloblastoma is generally iso- to hypointense, while on T2-weighted images, the densely packed cellular component of the tumor is significantly hypointense and displays restricted diffusion on diffusion-weighted imaging. Following intravenous gadolinium, medulloblastoma shows significant but variable and heterogeneous contrast enhancement. Given the propensity of neuraxial spread in medulloblastoma, sagittal fat-suppressed T1-postcontrast spinal MRI is recommended to rule out leptomeningeal metastases for accurate staging. Following neurosurgical excision, postoperative MRI done within 24-48h confirms the extent of resection, accurately quantifying residual tumor burden imperative for risk assignment. Post-treatment MRI is needed to assess response and effectiveness of adjuvant radiotherapy and systemic chemotherapy. After completion of planned therapy, surveillance MRI is recommended periodically on follow-up for early detection of recurrence for timely institution of salvage therapy, as well as for monitoring treatment-related late complications. Recent studies suggest that preoperative MRI can reliably identify SHH and Group 4 medulloblastoma but has suboptimal predictive accuracy for WNT and Group 3 tumors. In this review, we focus on the role of MRI in the diagnosis, staging, and quantifying residual disease; post-treatment response assessment; and periodic surveillance, and provide a brief summary on radiogenomics in the contemporary management of medulloblastoma.

Comparison of response assessment in veterinary neuro-oncology and two volumetric neuroimaging methods to assess therapeutic brain tumour responses in veterinary patients.

Standardized veterinary neuroimaging response assessment methods for brain tumours are lacking. Consequently, a response assessment in veterinary neuro-oncology (RAVNO) system which uses the sum product of orthogonal lesion diameters on 1-image section with the largest tumour area, has recently been proposed. In this retrospective study, 22 pre-treatment magnetic resonance imaging (MRI) studies from 18 dogs and four cats with suspected intracranial neoplasia were compared by a single observer to 32 post-treatment MRIs using the RAVNO system and two volumetric methods based on tumour margin or area delineation with HOROS and 3D Slicer software, respectively. Intra-observer variability was low, with no statistically significant differences in agreement index between methods (mean AI ± SD, 0.91 ± 0.06 for RAVNO; 0.86 ± 0.08 for HOROS; and 0.91 ± 0.05 for 3D slicer), indicating good reproducibility. Response assessments consisting of complete or partial responses, and stable or progressive disease, agreed in 23 out of 32 (72%) MRI evaluations using the three methods. The RAVNO system failed to identify changes in mass burden detected with volumetric methods in six cases. 3D Slicer differed from the other two methods in three cases involving cysts or necrotic tissue as it allowed for more accurate exclusion of these structures. The volumetric response assessment methods were more precise in determining changes in absolute tumour burden than RAVNO but were more time-consuming to use. Based on observed agreement between methods, low intra-observer variability and decreased time constraint, RAVNO might be a suitable response assessment method for the clinical setting.

Prediction of clinical response to corticosteroid or platelet-rich plasma injection in plantar fasciitis with MRI: A prospective, randomized, double-blinded study

PurposeThe purpose of this study was to identify association between magnetic resonance imaging (MRI) features and clinical data at baseline and six months following platelet-rich plasma (PRP) or corticosteroid (CS; cortivazol) injection in patients with plantar fasciitis, and to identify initial MRI criteria associated with a favorable clinical response to treatment. Material and methodsThe study was registered on ClinicalTrials.gov (NCT03857334). MRI examinations of 36 patients with plantar fasciitis lasting more than 3 months who were randomly assigned to receive ultrasound-guided PRP (PRP group, 20 patients) or CS (CS group, 18 patients) injection were quantitatively and qualitatively analyzed with respect to plantar fascia thickness, plantar fascia hyperintensity on T2-weighted STIR (HSTIR) images, calcaneal bone marrow and surrounding soft tissues. Clinical evaluation including visual analytic scale (VAS) assessment and MRI examinations were obtained before and 6 months after treatment. Good clinical response was defined as pain VAS decrease > 50% at 6 months. ROC curves with AUC measurements were used to determine cut-off points. ResultsIn the whole study population, an association was found between MRI features (deep soft tissue and calcaneal bone marrow HSTIR) and pain VAS scores for the first steps of the day (P = 0.028 and P = 0.007, respectively). No significant radioclinical associations on post-treatment MRI examinations were found in either group. Initial coronal thickness of plantar fascia was associated with a good clinical response in the CS group (P < 0.01). ROC curve analysis found that 7-mm or thicker plantar aponeurosis at initial MRI was predictive of good clinical response in patients with CS treatment (Youden index = 0.6). PRP infiltrations were effective regardless of fascia thickness (73% of patients with ≤ 7 mm aponeurosis and 67% for thicker ones). ConclusionInitial facia thickness (> 7 mm) is predictive of good clinical response six months after CS injection, whereas PRP injection shows effectiveness regardless of fascia thickness.

Pilot study of focused ultrasound for drug-resistant epilepsy.

ObjectiveThe neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal epilepsy models; however, the safety and efficacy of FUS in humans with epilepsy have not been well established. Patients with drug‐resistant epilepsy (DRE) undergoing stereo‐electroencephalography (SEEG) provide an opportunity to investigate the neuromodulatory effects of FUS in humans.MethodsPatients with DRE undergoing SEEG for localization of the seizure onset zone (SOZ) were prospectively enrolled. FUS was delivered to the SOZ using a neuronavigation‐guided FUS system (ceiling spatial‐peak temporal‐average intensity level = 2.8 W/cm2, duty cycle = 30%, modulating duration = 10 min). Simultaneous SEEG recordings were obtained during sonication and for 3 days after treatment. Seizures, interictal epileptiform discharges, and adverse events after FUS were monitored.ResultsSix patients met the eligibility criteria and completed FUS treatment. A decrease in seizure frequency was observed in two patients within the 3‐day follow‐up; however, one patient presented an increase in the frequency of subclinical seizures. Posttreatment magnetic resonance imaging revealed neither lesion nor brain edema. Significant changes in spectral power of SEEG were noted at the targeted electrodes during FUS treatment. One patient reported subjective scalp heating during FUS, and one patient developed transient naming and memory impairment that resolved within 3 weeks after FUS.SignificanceFUS can be safely delivered to the SOZ of patients with DRE, resulting in significant changes in spectral power of SEEG. A larger sample cohort and pursuing optimal sonication parameters will be required to elucidate the neuromodulatory effects of FUS when used for seizure control.

Yield of Surveillance Imaging in Long-Term Survivors of Brain Metastasis Treated With Stereotactic Radiosurgery

Although patients with brain metastasis treated with stereotactic radiosurgery (SRS) in the definitive or post-operative setting have high rates of local control, surveillance imaging is necessary to assess for central nervous system (CNS) recurrence. Guidelines recommend magnetic resonance imaging (MRI) of the brain every three months for surveillance in asymptomatic patients post-SRS. However, optimal frequency and duration of surveillance imaging in long-term survivors is unknown. Our objective is to define the yield and cost of surveillance MRIs in long-term (> 1 year) survivors following SRS.We identified a cohort of patients with brain metastases treated with SRS in the definitive or postoperative setting at a single institution from 8/2014 to 9/2019. Eligible patients had at least one-year of follow-up with absence of CNS disease failure up to and including the first MRI of the brain after 12 months from SRS. Each post-treatment MRI of the brain was assessed for disease progression or new lesions. CNS disease-free survival was time from SRS to last follow-up, death or CNS failure. Delay to diagnosis and cost per patient were estimated using hypothetical MRI schedules of 2, 3, 4 and 6 months from 1-year post-treatment while CNS disease-free. Delay to diagnosis was calculated as time from actual CNS progression to hypothetical imaging date. Medicare reimbursement median cost of $498 per MRI brain with and without contrast was used for this analysis.A total of 373 patients treated with SRS for brain metastasis were identified at our institution. 61 patients met eligibility criteria for inclusion in this study (median follow-up 2.50 years, median age at treatment 60 years). The median CNS disease-free survival in this population was 2.37 years from date of SRS. 15 patients (24.6%) had CNS progression at median time of 2.26 years. Of the 15 patients, 3 patients were symptomatic at recurrence. Median frequency of MRI after one year post SRS was 5.9 months. Per patient, $1156 was spent annually on MRIs of the brain after 12 months with average annual yield of 17.0%. The cost per diagnosis of CNS progression was $6806. A 2-month, 3-month, 4-month and 6-month MRI schedule had a respective estimated delay to diagnosis of 0.69 months, 1.13 months, 1.44 months and 3.19 months. The respective mean total cost of each MRI schedule per patient from one-year post-treatment while CNS disease-free was $4662, $3053, $2229 and $1380.Patients with metastatic disease to the brain treated definitively or postoperatively with SRS without evidence of CNS recurrence at one year have a low rate of CNS failure and relatively good prognosis. Based strictly on limiting delay of diagnosis, a 2-month MRI Brain schedule is optimal in this population, albeit with a relatively small increase in financial cost over the patient's lifespan. We propose a multi-institutional study of long-term survivors with brain metastasis to strengthen these findings.B.J. Rich: None. D. Kwon: None. Y.S. Soni: None. D.L. John: None. J.B. Bell: None. G. Azzam: None. E.A. Mellon: None. R. Yechieli: Support and guide school in strategic and management related matters; Toras Chaim Toras Emes, Miami FL.C. Benjamin: None. R. Benveniste: None. R.J. Komotar: None. M. Ivan: None. J. Morcos: None. T. Diwanji: None.

Artificial intelligence for early prediction of treatment response in glioblastoma

Abstract Aims Treatment response assessment in glioblastoma is challenging. Patients routinely undergo conventional magnetic resonance imaging (MRI), but it has a low diagnostic accuracy for distinguishing between true progression (tPD) and pseudoprogression (psPD) in the early post-chemoradiotherapy time period due to similar imaging appearances. The aim of this study was to use artificial intelligence (AI) on imaging data, clinical characteristics and molecular information within machine learning models, to distinguish between and predict early tPD from psPD in patients with glioblastoma. Method The study involved retrospective analysis of patients with newly-diagnosed glioblastoma over a 3.5 year period (n=340), undergoing surgery and standard chemoradiotherapy treatment, with an increase in contrast-enhancing disease on the baseline MRI study 4-6 weeks post-chemoradiotherapy. Studies had contrast-enhanced T1-weighted imaging (CE-T1WI), T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences, acquired at 1.5 Tesla with 6-months follow-up to determine the reference standard outcome. 76 patients (mean age 55 years, range 18-76 years, 39% female, 46 tPD, 30 psPD) were included. Machine learning models utilised information from clinical characteristics (age, gender, resection extent, performance status), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and 307 quantitative imaging features; extracted from baseline study CE-T1WI/ADC and T2WI sequences using semi-automatically segmented enhancing disease and perilesional oedema masks respectively. Feature selection was performed within bootstrapped cross-validated recursive feature elimination with a random forest algorithm and Naïve Bayes five-fold cross-validation to validate the final model. Results Treatment response assessment based on the standard-of-care reports by clinical neuroradiologists showed an accuracy of 33% (sensitivity/specificity 52%/3%) to distinguish between tPD and psPD from the early post-treatment MRI study at 4-6 weeks. Machine learning-based models based on clinical and molecular features alone demonstrated an AUC of 0.66 and models using radiomic features alone from the early post-treatment MRI demonstrated an AUC of 0.46-0.69 depending on the feature and mask subset. A combined clinico-radiomic model utilising top common features demonstrated an AUC of 0.80 and an accuracy of 74% (sensitivity/specificity 78%/67%). The features in the final model were age, MGMT promoter methylation status, two shape-based features from the enhancing disease mask (elongation and sphericity), three radiomic features from the enhancing disease mask on ADC (kurtosis, correlation, contrast) and one radiomic feature from the perilesional oedema mask on T2WI (dependence entropy). Conclusion Current standard-of-care glioblastoma treatment response assessment imaging has limitations. In this study, the use of AI through a machine learning-based approach incorporating clinical characteristics and MGMT promoter methylation status with quantitative radiomic features from standard MRI sequences at early 4-6 weeks post-treatment imaging showed the best model performance and a higher accuracy to distinguish between tPD and psPD for early prediction of glioblastoma treatment response.

Determinants and Outcomes of Asymptomatic Intracranial Atherosclerotic Stenosis

BackgroundIntracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive management of risk factors. ObjectivesThis study identified the role of risk factors and risk of vascular events in subjects with asymptomatic ICAS for improved risk stratification. MethodsStroke-free participants in the NOMAS (Northern Manhattan Study), prospectively followed since 1993, underwent a brain magnetic resonance angiogram from 2003 to 2008. The study rated stenosis in 11 brain arteries as: 0: no stenosis; 1: <50% or luminal irregularities; 2: 50%-69%; and 3: ≥70% stenosis or flow gap. The study ascertained vascular events during the post-magnetic resonance imaging (MRI) period. Proportional odds regression quantified the association of pre-MRI exposures, and proportional hazard adjusted models were built to identify the risk of events in the post-MRI period. ResultsThe included sample included 1,211 participants from NOMAS (mean age: 71 ± 9 years; 59% women; 65% Hispanic; 45% had any stenosis). Older age (OR: 1.02 per year; 95% CI: 1.01 to 1.04), hypertension duration (OR: 1.01 per year; 95% CI: 1.00 to 1.02), higher number of glucose-lowering drugs (OR: 1.64 per each medication; 95% CI: 1.24 to 2.15), and high-density lipoprotein (OR: 0.96 per mg/dL; 95% CI: 0.92 to 0.99) were associated with ICAS. The highest event risk was noted among participants with ICAS ≥70% (5.5% annual risk of vascular events; HR: 2.1; 95% CI:1.4 to 3.2; compared with those with no ICAS). ConclusionsICAS is an imaging marker of established atherosclerotic disease in stroke-free subjects, and incidental diagnosis of ICAS should trigger a thorough assessment of vascular health.

Percutaneous MR Imaging-Guided Laser Ablation and Cryoablation for the Treatment of Pediatric and Adult Symptomatic Peripheral Soft Tissue Vascular Anomalies

PurposeTo evaluate the safety and effectiveness of percutaneous magnetic resonance (MR) imaging-guided laser ablation and cryoablation for the treatment of symptomatic soft tissue vascular anomalies (VAs) of the trunk and extremities. Materials and MethodsAn institutional review board-approved retrospective review was undertaken of all pediatric and adult patients who underwent MR imaging-guided and monitored laser ablation and/or cryoablation for the treatment of symptomatic peripheral soft tissue VA. Preablation and postablation MR imaging was independently reviewed. Pain scores on the visual analog scale (0 to 10) and self-reported subjective symptomatic improvement were assessed. Change in VA size and pain scores were compared using a paired t test. ResultsThirty patients (24 females; age, 10–75 years) with 34 VAs were treated for moderate to severe pain (n = 27) or swelling/mass effect (n = 3) with 60 total ablation sessions. The baseline maximum VA diameter was 9.5 cm ± 8.6. At baseline, all VAs (100%) demonstrated variable T2-weighted signal hyperintensity and enhancement. The baseline pain score was 6.4 ± 1.6. Clinical follow-up was available for 23 patients. At a mean follow-up time of 12.2 months ± 10.1, 19 of 20 (95%) patients treated for pain and 2 of 3 (67%) patients treated for swelling/mass effect reported partial or complete symptomatic relief. There was a significant decrease in the postablation pain scores (−5.7 ± 1.0, P < .001) and maximum VA size (−2.3 cm ± 2.7, P = .004), with >50% reduction in VA T2 signal (59%) and enhancement (73%). Nine of 30 (30%) patients experienced minor complications. ConclusionsMR imaging-guided and monitored percutaneous laser ablation and cryoablation appear to be safe and effective for the treatment of symptomatic peripheral soft tissue VAs.

Efficacy of intravenous neridronate in transient osteoporosis of the hip.

To evaluate the efficacy and safety of intravenous (iv) neridronate in patients affected by transient osteoporosis of the hip (TOH). We retrospectively evaluated the clinical records of patients affected by TOH treated with iv neridronate in our department. We treated patients with a value of visual analogue scale (VAS)-pain ≥ 80/100 mm at diagnosis, limited range of movement and magnetic resonance images (MRI) findings suggestive of TOH. The regimen used was: one iv infusion at day 0, 3, 6, 9 (100 mg for each infusion: total of 400 mg). This protocol was repeated in refractory cases. Recovery was defined as VAS-pain level ≤20/100. Concomitant use of analgesics was allowed. Paired Student t-test was used to assess VAS-pain change. Five patients were male, 3 were female. Mean age was 54.5±2.12 years old. Mean body mass index was 26.57±2.22. Mean time to diagnosis, since the onset of the symptoms, was 75±21.21 days. Mean number of neridronate infusions was 7.5±2.56. Mean time of recovery was 57±45.96 days. Mean VAS-pain at baseline was 84±2,24. Mean VAS-pain after treatment was significantly reduced (p<0.001) with a value of 12.12±6.46. None of the patients needed analgesics after treatment. No adverse event was reported. In 5 cases, post-treatment MRI showed complete bone marrow oedema resolution. Intravenous neridronate is effective and safe in the treatment of TOH and its use may lead to a faster resolution of the disease.

Transanal approach after preoperative imatinib treatment of a rectal gastrointestinal stromal tumors with external anal sphincter invasion: A case report.

Introduction and importanceRectal gastrointestinal stromal tumors (GISTs) are rare, and preserving anorectal function can be challenging. We report the case of a patient with rectal GIST with external anal sphincter invasion, treated via the laparoscopic and transanal approaches.Case presentationA 61-year-old man with locally advanced GIST in the right anterolateral wall of the lower rectum was examined. Lower endoscopy revealed a 50-mm submucosal tumor located 4 cm from the anal verge. On immunohistochemistry, the biopsy specimen tested positive for CD34 and C-KIT, and the patient was diagnosed with GIST. Abdominal magnetic resonance imaging (MRI) revealed external anal sphincter infiltration. Because of the large tumor size and proximity to the anal verge, preserving the anus was challenging, and colorectal resection was avoided. Instead, neoadjuvant therapy with imatinib was administered to facilitate local resection of the tumor. Post-treatment MRI showed a reduction in tumor size (30 × 20 × 30 mm), and surgery was performed. We identified an appropriate resection line for diplomatic sphincter resection of the infiltrated area by laparoscopy alone. Thus, we performed a hybrid surgery using the laparoscopic and transanal approaches. The patient had an unremarkable postoperative course and was discharged on postoperative day 23.Clinical discussionNo study has reported cases of rectal GIST with external anal sphincter invasion wherein anal function was preserved. Here, imatinib was administered preoperatively, and hybrid surgery was performed using the transanal and laparoscopic approaches.ConclusionPreoperative treatment and surgery preserved anorectal function in a patient with a massive rectal GIST.

Abstract 1782: Acidovorax temperans modulates the host immune microenvironment to promote lung cancer development

Abstract Lung cancer is the most common cause of cancer-related death worldwide in both men and women. The overall survival of lung cancer remains poor due to limitations in diagnostic and therapeutic strategies. Therefore, the development of novel biomarkers is urgently needed to improve patient prognosis. Growing evidence has demonstrated alterations of the normal microbiome in lung cancer. Dysbiosis may alter normal microbiota-host interactions and induce immune dysregulation, and therefore contribute to the promotion of tumorigenesis. Although multiple studies show an association between dysbiosis, host immune response and tumorigenesis, the underlying mechanisms are still unclear. We previously characterized a distinct group of taxa that are enriched in lung adenocarcinoma and squamous cell carcinoma. Among these taxa, Acidovorax spp. were associated with cigarette smoking and TP53 mutations, with Acidovorax temperans identified by full-length 16S sequencing. We hypothesized that enrichment of A. temperans in the lung microbial community may modulate the immune microenvironment and therefore contribute to tumor development. We used an autochthonous mouse model of lung adenocarcinoma, in which tumorigenesis is driven by oncogenic K-Ras and a gain-of function mutant p53 under the control of the Cre-lox system. We administered biweekly intranasal instillations of A. temperans to mimic the effects of chronic tobacco smoking. Following bacterial instillation, the lung tumor development was determined by magnetic resonance imaging (MRI) at 13 weeks post Ad-Cre instillation. Mice challenged with A. temperans exhibited significantly larger tumor burden and a deleterious effect on survival compared to the sham group. Given the importance of the immune system in modulating tumor development, we then investigated whether A. temperans exposure induced changes in the immune microenvironment through high parametric flow cytometry post 5th instillation and post MRI. Lungs from mice instilled with A. temperans showed an increased number of total leukocytes. The vast majority of leukocytes were pro-inflammatory cells and predominantly neutrophils. Moreover, we also found an increase in CD4+ T cells and double negative T cells, and an increase in RORγt+/IL17+ subpopulations in both of these T cell groups. Consistent with these results, the IL-17 expression level was upregulated in response to A. temperans instillation. Taken together, these results indicate that A. temperans exposure induces a robust pro-inflammatory response, thereby increasing immune infiltration in the tumor microenvironment and promoting development of lung adenocarcinoma. Citation Format: Chenran Zhang, Natalia von Muhlinen, Araya Romina, Joshua Stone, Romina Goldszmid, Curtis Harris. Acidovorax temperans modulates the host immune microenvironment to promote lung cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1782.

Pre-Clinical Study of Ibrutinib for the Treatment of T-Cell Lymphoma Using Magnetic Resonance Imaging (MRI) Assessment

Peripheral T cell lymphoma (PTCL) has a poor prognosis and there is a need for new treatments.The sanroque mouse bears a mutation in the E3 ubiquitin ligase, Roquin, which leads to T-cell activation and autoimmunity in homozygous animals. In heterozygous mice (Roquinsan/+) T-cell lymphomas with histological similarity to human angioimmunoblastic lymphoma (AITL), the commonest subtype of PTCL, develop in 40 to 50% of animals by 6 - 12 months of age.In order to test the feasibility of using sanroque mice for pre-clinical work we carried out MRI scans of the axillary and inguinal regions before and after receiving 200mg/kg cyclophosphamide as an intra-peritoneal injection. After 28-days the MRI scans were repeated and lymph nodes, spleens and livers collected.MRI scanning was performed on a 9.4T Agilent scanner (Agilent Technologies, Santa Claire, CA, USA) with a 310mm bore diameter and 6cm inner-diameter gradient (1000mT/m maximum gradient strength). A 4cm millipede RF coil was used for RF transmission and reception. T2-weighted images were acquired using a respiratory-gated fast spin echo (FSE) sequence with TR/TE=3000/40ms, 40x40mm field of view (256x256 matrix), 32x0.8mm slices and two signal averages.Enlarged lymph nodes were identified on the pre-treatment MRI scan and compared to the equivalent lymph node following treatment (Figure 1A). There was a mean 94% reduction in lymph node size following cyclophosphamide treatment. This demonstrated that the enlarged lymph nodes were chemosensitive and that MRI scanning could be used to monitor the lymph node size in response to treatment.Interleukin-2-inducible kinase (ITK) is expressed and has essential functions in regulating normal T-cell proliferation and differentiation. ITK is also expressed in AITL and might be a therapeutic target but there is no pre-clinical data. The small molecule BTK/ITK inhibitor, ibrutinib, is effective and well tolerated in clinical practice in some B-cell lymphomas and ibrutinib is active against mouse ITK.In order to assess the effect of ibrutinib on (Roquinsan/+) T-cell lymphoma we identified twelve mice with palpable lymph nodes. Following an MRI scan, oral treatment with ibrutinib (25mg/kg in 1% (2-Hydroxypropyl)-β-cyclodextrin (2HPBD)) or equivalent volume of vehicle (1% 2HPBD) was given daily by gavage. Five mice were treated with ibrutinib for 28 days and three for reduced time periods (7 days, 14 days and 21 days). Four mice were treated with vehicle for 28 days. Following cessation of therapy a further MRI scan was performed prior to harvesting of tissues, including liver, spleen and lymph nodes. MRI images were analysed to determine the change in volume of lymph nodes during the treatment period.Responses to ibrutinib were mixed (Figure 1B & 1C): of those that received 28 days treatment 5/8 animals showed reduction in tumour size of between 10 and 86% whilst those that received shorter durations of treatment showed reductions of 8 and 11%. 3/8 ibrutinib treated animals showed increases in tumour size of 9 and 85% (mice treated for 28 days) whilst one animal treated for 7 days showed an increase of 117%. 3/4 vehicle treated animals showed stable or increasing lymphadenopathy whilst one mouse showed spontaneous tumour regression.In order to analyze the effects of ibrutinib at the cellular level we established flow cytometry protocols to determine cellular composition. Previous reports show that the majority of cells within sanroque enlarged lymph nodes are B-cells with a minority (1 to 2%) being malignant T-cells. This is similar to the pattern observed in human Tfh lymphoma. Lymph nodes were harvested following the post-treatment MRI scan and cell suspensions produced. The proportions of CD4+, CD8+ and B220+ lymphocytes were assessed. To determine the Tfh cell population CD4 positive lymphocytes were gated and the proportion of CXCR5hiPD1hi cells assessed. We did not observe any significant differences between responding and non-responding mice (Figure 1D) or treated and untreated mice.We have developed an MRI protocol to assess the response of a T-cell lymphoma model to novel agents to facilitate pre-clinical studies. We interpret our results as showing that ibrutinib is effective as a single agent in a proportion of the spontaneous T-cell lymphomas generated in the Roquinsan/+ model of Tfh lymphoma but further work is required to understand the differences between responder and non-responder tumours. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

MRI in head and neck cancer following chemoradiotherapy: what is the optimal delay to demonstrate maximal response?

ObjectivesTo investigate the optimal timing for post-chemoradiotherapy (CRT) reference magnetic resonance imaging (MRI) in head and neck cancer, so as to demonstrate a maximal treatment response. To assess whether this differs in human papillomavirus–related oropharyngeal cancer (HPV-OPC) and whether the MRI timing impacts on the ability to predict treatment success.MethodsFollowing ethical approval and informed consent, 45 patients (40 male, mean age 59.7 ± 7.9 years, 33 HPV-OPC) with stage 3 and 4 HNSCC underwent pre-treatment, 6- and 12-week post-CRT MRIs in this prospective cohort study. Primary tumour (n = 39) size, T2w morphology and diffusion weight imaging (DWI) scores, together with nodal (n = 42) size and necrotic/cystic change, were recorded. Interval imaging changes were analysed for all patients and according to HPV-OPC status. MRI descriptors and their interval changes were also compared with 2-year progression-free survival (PFS).ResultsAll MRI descriptors significantly changed between pre-treatment and 6-week post-treatment MRI studies (p < .001). Primary tumour and nodal volume decreased between 6- and 12-week studies; however, interval changes in linear dimensions were only evident for HPV-OPC lymph nodes. Nodal necrosis scores also evolved after 6 weeks but other descriptors were stable. The 6-week nodal necrosis score and the 6- and 12-week nodal volume were predictive of 2-year PFS.ConclusionApart from HPV-OPC patients with nodal disease, the 6-week post-CRT MRI demonstrates maximal reduction in the linear dimensions of head and neck cancer; however, a later reference study should be considered if volumetric analysis is applied.Key Points• This study provides guidance on when early post-treatment imaging should be performed in head and neck cancer following chemoradiotherapy, in order to aid subsequent detection of recurrent tumour.• Lymph nodes in HPV-related oropharyngeal cancer patients clearly reduced in size from 6 to 12 weeks post-treatment. However, other lymph node disease and all primary tumours showed only a minor reduction in size beyond 6 weeks, and this required a detailed volumetric analysis for demonstration.• Timing of the reference MRI following chemoradiotherapy for head and neck cancer depends on whether the patient has HPV-related oropharyngeal cancer and whether there is nodal disease. MRI as early as 6 weeks post-treatment may be performed unless volumetric analysis is routinely performed.

Does the primary soft-tissue sarcoma configuration predict configuration of recurrent tumors on magnetic resonance imaging?

Soft-tissue sarcomas (STS) are rare malignancies of the soft tissue. To assess whether the magnetic resonance imaging (MRI) configuration of primary STS can predict the configuration of a recurring tumor and whether the MRI configuration of multiple recurrences differs in one and the same patient. Thirty-nine patients with histologically proven recurrent STS were included in this retrospective study and underwent pre- and post-treatment MRI. Three main configurations of primary and recurrent tumors were identified: polycyclic/multilobulated; ovoid/nodular; and streaky. Sixty recurrent lesions were detected: 34 ovoid/nodular; 15 polycyclic/multilobulated; and 11 streaky. Five recurrences were multifocal and eight were bifocal. Of 39 patients, 28 (71.8%) presented one recurrence within the MRI follow-up period (P = 0.006); in 10 patients (25.6%), up to three different configurations of recurring STS were identified in one patient. Recurrences of polycyclic/multilobulated primaries were mostly ovoid/nodular (48%; P = 0.003) or polycyclic/multilobulated (37%; P = 0.014), and recurring ovoid/nodular STS significantly most often showed the same configuration as the primary tumor (85%; P < 0.001). Primary STS with a streaky configuration recurred in all three configurations in roughly equal proportions. Homogeneity/heterogeneity and tumor borders are significantly associated with the configuration of recurrences. Primary STS configuration may help predict recurrent tumor configuration when the primary STS had a polycyclic/multilobulated or ovoid/nodular configuration. However, recurrent STS configuration can also differ from primary STS configuration, especially when the primary STS had a streaky configuration, rendering recurrent STS difficult to predict. Different configurations of recurrent STS in one and the same patient are common.

Accuracy of breast MRI in evaluating nodal status after neoadjuvant therapy in invasive lobular carcinoma

Neoadjuvant therapy in breast cancer can downstage axillary lymph nodes and reduce extent of axillary surgery. As such, accurate determination of nodal status after neoadjuvant therapy and before surgery impacts surgical management. There are scarce data on the diagnostic accuracy of breast magnetic resonance imaging (MRI) for nodal evaluation after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), a diffusely growing tumor type. We retrospectively analyzed patients with stage 1–3 ILC who underwent pre-operative breast MRI after either neoadjuvant chemotherapy or endocrine therapy at our institution between 2006 and 2019. Two breast radiologists reviewed MRIs and evaluated axillary nodes for suspicious features. All patients underwent either sentinel node biopsy or axillary dissection. We evaluated sensitivity, specificity, negative and positive predictive values, and overall accuracy of the post-treatment breast MRI in predicting pathologic nodal status. Of 79 patients, 58.2% received neoadjuvant chemotherapy and 41.8% neoadjuvant endocrine therapy. The sensitivity and negative predictive value of MRI were significantly higher in the neoadjuvant endocrine therapy cohort than in the neoadjuvant chemotherapy cohort (66.7 vs. 37.9%, p = 0.012 and 70.6 vs. 40%, p = 0.007, respectively), while overall accuracy was similar. Upstaging from clinically node negative to pathologically node positive occurred in 28.0 and 41.7%, respectively. In clinically node positive patients, those with an abnormal post-treatment MRI had a significantly higher proportion of patients with ≥4 positive nodes on pathology compared to those with a normal MRI (61.1 versus 16.7%, p = 0.034). Overall, accuracy of breast MRI for predicting nodal status after neoadjuvant therapy in ILC was low in both chemotherapy and endocrine therapy cohorts. However, post-treatment breast MRI may help identify patients with a high burden of nodal disease (≥4 positive nodes), which could impact pre-operative systemic therapy decisions. Further studies are needed to assess other imaging modalities to evaluate for nodal disease following neoadjuvant therapy and to improve clinical staging in patients with ILC.

Analysis of rectal dose during prostate stereotactic body radiotherapy in MR-guided radiotherapy.

242 Background: The Unity MR-Linac combines a 7-MV Linac with 1.5T magnetic resonance (MR) imaging capability and it enables adaptive radiotherapy, whereby the target and organs at risk are recontoured and a plan is optimised daily. During treatment a session MR image is taken first, on which the target and organs-at-risk are contoured, and a plan created. A verification image is taken prior to dose delivery to identify intra-fractional changes. If present, the daily treatment plan is shifted to reflect the anatomy. A post-treatment image is acquired at the end of treatment. This study evaluates the dosimetric changes to the rectum caused by intra-fractional changes during treatment delivery for prostate stereotactic body radiotherapy (SBRT) calculated on the verification and post-treatment images. Methods: The first five patients treated on the MR-Linac with 5-fraction SBRT to the prostate are included in this study. For each patient, the rectum was contoured on the verification and post-treatment MR images for each of the five fractions. The dose delivered to the rectum with the original treatment plan was then calculated on each image and the V36Gy rectal dose constraint was noted. Results: Out of the 25 fractions, a post treatment image was not performed in one fraction; 24 fractions were therefore analysed in total. The rectal V36Gy dose constraint exceeded the mandatory target of 2cc on 50% of the verification images and 46% of the post-treatment images. In 6 fractions the rectal V36Gy was greater than 2cc on both the verification and post-treatment images suggesting this rectal constraint was exceeded throughout treatment. In 17% of patients, the volume of rectum receiving 36Gy increased at each timepoint an image was taken during the treatment workflow. Conclusions: The rectal V36Gy dose constraint is susceptible to minor changes in rectal filling, which may often lead to higher than the accepted dose constraint. Thus, a single planning CT scan is unlikely to be representative of dose delivered. Adaptive radiotherapy can reduce this uncertainty somewhat, but intra-fraction dose re-optimisation would be required to ensure the rectal V36Gy remains acceptable at all times.

Abstract PS3-09: The use of magnetic resonance imaging (MRI) in predicting pathological complete response(pCR) in the breast and axilla after the addition of immunotherapy to neoadjuvant systemic therapy (NST)

Abstract Introduction: Immunotherapy use is increasing as an adjunct to current NST for breast cancer treatment with the goals of increasing pCR and down staging tumors. In this study, we assessed the effectiveness of MRI in the evaluation of tumor response after neoadjuvant immunotherapy in combination with NST. Methods: We retrospectively reviewed the clinicopathological data of 105 women undergoing Immunotherapy in conjunction with NST at a single institution. All patients had been enrolled in IRB approved protocols and had undergone definitive surgery. Patients were excluded for: failure to complete at least two thirds of treatment, no pre or post treatment MRI, or surgery in an outside institution. We analyzed 73 patients from 5 distinct treatment protocols including: (1) 24 Triple negative breast cancer (TNBC) patients (pts) treated with Intratumoral Talimogene laherparepvec (TVEC) in combination with weekly paclitaxel followed by dose dense Adriamycin and Cytoxan (ddAC); (2) 19 HER2/Neu positive (HER2+) pts treated with subcutaneous interferon gamma (IFN-γ) in combination with weekly paclitaxel with trastuzumab and pertuzumab (HP); (3), 7 HER2+ pts treated with 3 weeks of HER2 pulsed dendritic cell vaccines (DC1) followed by Taxotere, Carboplatin, and HP; (4), 14 pts on the ISPY2 trial: 8 TNBC and 4 Hormone receptor positive, HER2/Neu negative (HR+) pts randomized to treatment with pembrolizumab with weekly paclitaxel followed by ddAC (2 also received additional SD101), and 2 TNBC pts treated with Durvalumab, Olaparib and Paclitaxel, followed by ddAC and (5) 9 HR+ pts on neoadjuvant Durvalumab and an Aromatase Inhibitor for 6 cycles. Results: A total of 73 patients were included in the study. Median age was 51 years (range 27-76); 46.6% of patients had TNBC, 35.6% had HER2+ and the remaining 17.8% were HR+ HER2-. The median clinical tumor size was 3.4cm (range 1.3-10.6) pre therapy and 1cm (range 0-10.1) post therapy. The pCR was 38.2%, 57.7%, and 0% respectively for TNBC, HER2+, HR+ tumors. Complete radiological response (rCR) of both the axilla and breast was 41.2%, 61.5% and 7.7%, for TNBC, HER2+ and HR+ tumors. The sensitivity of MRI to detect in breast pCR was 65.6% with a specificity of 81%, NPV and PPV of 75% and 73.3% respectively. MRI identified 37 pts with suspicious axillary nodes on pretreatment MRI; of these 30 had fine needle aspiration (FNA) confirmed metastatic disease. Post treatment, 70.3% (26/37) had normalized axillary nodes. Of those with normalized nodes, 26.9% (7/26) had residual cancer on final pathology. Of the patients with confirmed FNA lymph node metastasis, axillary pCR of 63.3% was achieved. The sensitivity and specificity of MRI to detect pCR within the axilla was 87% and 50% and NPV and PPV 70% and 74.1%, respectively. 3 patients had axillary disease on final pathology but no suspicious imaging and a benign FNA. Conclusion: The addition of immunotherapy to current NST strategies can improve pCR and decrease residual cancer burden. The PPV and NPV of MRI to predict pCR in patients undergoing immunotherapy in combination with NST remains within the ranges described in patients undergoing NST alone. MRI remains a useful tool to guide surgical management but is not accurate enough to replace pathological evaluation. Citation Format: Noeline Rajarajan, Daniel Segarra, Robert J Weinfurtner, Adrian A Lopez, M Catherine Lee, John Kiluk, Hatem Soliman, Hung Khong, Han S Hyo, Marilin Rosa, Brian J Czerniecki, Nazanin Khakpour. The use of magnetic resonance imaging (MRI) in predicting pathological complete response(pCR) in the breast and axilla after the addition of immunotherapy to neoadjuvant systemic therapy (NST) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-09.

Liproca Depot: A New Antiandrogen Treatment for Active Surveillance Patients

BackgroundThere is increasing interest in nonmorbid treatments for low- and intermediate-risk prostate cancer with fewer side effects than surgery or radiotherapy. ObjectiveTo investigate the tolerability, safety, and antitumor effects of the intraprostatic NanoZolid depot formulation Liproca Depot (LIDDS AB, Uppsala, Sweden) with antiandrogen 2-hydroxyflutamide (2-HOF) in men with low- or intermediate-risk localized prostate cancer managed with active surveillance. Design, setting, and participantsThis clinical phase 2b trial, LPC-004, involved 61 patients. The 2-HOF-containing formulation Liproca Depot was injected transrectally into the prostate under ultrasound guidance. A single dose of 35% or 45% of the prostate volume (study part 1) and a fixed dose of 16 or 20 ml (study part 2) of the formulation were evaluated. Outcome measurements and statistical analysesThe primary endpoints were tolerability and the reduction in serum prostate-specific antigen (PSA) 5 mo after injection. Antitumor effects were evaluated with magnetic resonance imaging (MRI) and prostate biopsies. Quality of life was assessed using a validated questionnaire (International Prostate Symptom Score). Results and limitationsAll doses were safe and well tolerated, without hormonal side effects. In part 2 of the study, the PSA reduction was greatest for the group receiving 16 ml, with an average decrease of 14%, and 95% of patients had a PSA reduction. Some 78% of patients showed a prostate volume decrease compared to baseline. Prostate MRI and biopsies confirmed stable or reduced lesion size. However, post treatment biopsies were performed at the discretion of the investigator, and not routinely. Most patients were amenable to a second injection. ConclusionsPSA and prostate volume decreased in most patients. Indications of efficacy were shown by post-treatment MRI and biopsies demonstrating stabilization or regression in the majority of cases. Patient summaryLiproca Depot is a safe, minimally invasive treatment that offers the potential for cancer control in patients with intermediate-risk prostate cancer. Further clinical evaluation is warranted.