MRI features that predict progression of residual disease after ablation of extra-abdominal desmoid fibromatosis

Background Prostatic ductal adenocarcinoma (DAC) is an aggressive histologic variant of prostate cancer that often warrants multimodal therapy and poses a significant diagnostic challenge clinically and at imaging. Purpose To develop multiparametric MRI criteria to define DAC and to assess their diagnostic performance in differentiating DAC from prostatic acinar adenocarcinoma (PAC). Materials and Methods Men with histologically proven DAC who had multiparametric MRI before radical prostatectomy were retrospectively identified from January 2011 through November 2018. MRI features were predefined using a subset of nine DACs and then compared for men with peripheral-zone DACs 1 cm or greater in size and men with matched biopsy-confirmed International Society of Urological Pathology grade group 4-5 PAC, by four independent radiologists blinded to the pathologic diagnosis. Diagnostic performance was determined by consensus read. Patient and tumor characteristics were compared by using the Fisher test, t-tests, and Mann-Whitney U test. Agreement (Cohen κ) and sensitivity analyses were also performed. Results There were 59 men with DAC (median age, 63 years [interquartile range, 56, 67 years]) and 59 men with PAC (median age, 64 years [interquartile range, 59, 69 years]). Predefined MRI features, including intermediate T2 signal, well-defined margin, lobulation, and hypointense rim, were detected in a higher proportion of DACs than PACs (76% [45 of 59] vs 5% [three of 59]; P < .001). On consensus reading, the presence of three or more features demonstrated 76% sensitivity, 94% specificity, 94% positive predictive value [PPV], and 80% negative predictive value [NPV] for all DACs and 100% sensitivity, 95% specificity, 81% PPV, and 100% NPV for pure DACs. The DACs and PACs showed no difference in contrast enhancement (100% vs 100%; P >.99, median T2 signal intensity (254 vs 230; P = .99), or apparent diffusion coefficient (median, 677 10-6 mm2/sec vs 685 10-6 mm2/sec; P = .73). Conclusion The presence of intermediate T2 signal, well-defined margin, lobulation, and/or hypointense rim, together with restricted diffusion and contrast enhancement at multiparametric MRI of the prostate, suggests prostatic ductal adenocarcinoma rather than prostatic acinar adenocarcinoma. © RSNA, 2022 Online supplemental material is available for this article.

e17532 Background: Ductal prostate adenocarcinoma (DAC) is an aggressive histologic variant of prostate cancer (PCa) which often be missed due to their low PSA secretion. Further, a large proportion of DACs have extra-prostatic extension and nodal disease at presentation warranting accurate diagnosis and treatment planning. However studies have yet to differentiate DACs from high grade acinar PCas (PAC) on MRI. Therefore we aimed to develop MRI criteria to identify DACs and assess its diagnostic accuracy. Methods: Patients with histologically proven DAC who had MRIs prior to RP were identified from January 2011 to November 2018. Histology-based MRI diagnostic criteria were developed using RP specimens from nine patients with a pure dominant DAC focus and corresponding MRIs. Sixty-eight DAC patients were compared to a matched cohort of 70 patients with Gleason Score 8 or 9 PAC using the pre-defined MRI criteria. Chi-Squared, T tests, Mann Whitney U tests and sensitivity analyses were performed. Results: The following features of DAC were defined on MRI after correlation with histology: 1) intermediate T2 signal 2)well-circumscribed 3) lobulated tumor and 4) a dark peripheral rim. Majority of DACs were lobulated (79.4% vs 5.7%), with a dark peripheral rim on T2 weighted imaging (55.9% vs 4.3%) and had ≥3 MRI features compared to PAC (73.6% vs 7.2%) (all p &lt; 0.001). Moreover, a higher proportion of pure DACs were lobulated (100% vs 5.7%), had a dark peripheral rim (94.7% vs 4.3%) and ≥3 MRI features (100% vs 7.2%) compared to PAC (all P &lt; 0.001). There were no differences in median T2 contrast enhancement, ADC values or ADC ratios between the groups. Using our criteria MRI demonstrated sensitivity of 73.5%, specificity of 92.9 %, PPV of 90.9%, and NPV of 78.3% in diagnosing DACs if ≥3 features were present. In the diagnosis of pure DACs, MRI demonstrated sensitivity of 100%, specificity of 92.9%, PPV of 95.2%, and NPV of 100%. The area under the curve (AUC) for the diagnosis of all DACs was 0.81 and 0.98 for pure DACs. Conclusions: The presence of ≥3 features (well-circumscribed, lobulations and a dark peripheral rim and intermediate signal on the T2 phase) on prostatic MRI can help differentiate DAC from PAC. While this is the largest cohort of DACs to be analyzed, further studies are needed to validate these findings.

From an imaging perspective, desmoid tumors are best classified as extra-abdominal, abdominal wall, and intra-abdominal. MRI is the imaging modality of choice for extra-abdominal desmoids, demonstrating a lesion that can be well-defined, has infiltrative margins, or a combination of both. The lesions are low in T1 signal, while T2 signal is variable, depending upon the stage of evolution. During their early growth stage, desmoid tumors are highly cellular with relatively less collagen. As a result, they are predominantly high in T2 signal with small foci of low T2 signal, and demonstrate avid contrast enhancement. As they evolve over time, the tumors become less cellular and more densely collagenous, with a resultant decrease in T2 signal intensity and enhancement, and often with a concomitant decrease in size. Radiation and medical therapy can also result in these signal changes, suggesting treatment response even in the absence of decreases in size. Abdominal wall desmoid tumors can best be imaged with MRI or CT, while intra-abdominal desmoid tumors are best imaged with CT. CT demonstrates a mass which is nearly isodense to muscle on noncontrast images and which demonstrates mild-to-moderate enhancement with intravenous contrast. CT is superior to MRI in distinguishing intra-abdominal desmoids from adjacent bowel loops, although vascular involvement can be accurately assessed with either CT or MRI. MRI is sometimes desirable to CT for imaging of intra-abdominal desmoids, particularly in patients who cannot receive iodinated contrast material, either because of allergies or impaired renal function, or in patients in whom radiation exposure is a major concern. In patients with severe renal dysfunction, intravenous contrast should not be used with MRI either because of the risk of developing nephrogenic systemic sclerosis.

A thirty-three-year-old male presented to an outside emergency department with scrotal swelling and pain after intercourse. A scrotal ultrasound revealed hematoma, with no other abnormalities and the patient was discharged. He then presented to our institution where examination showed diffuse ecchymosis through the shaft of the penis, suprapubic region, and scrotum without a palpable cavernosal defect. Magnetic resonance imaging (MRI) without contrast was obtained after the injection of 10 micrograms of intracavernosal alprostadil. The low signal tunica albuginea is easily demarcated compared to the high T2 and intermediate T1 signal of the corpora cavernosum (Figures 1-3) (1,2). Hematoma shows heterogeneous intermediate T1 and T2 signal (Figures 2 and 3) (1). Penile fracture is rupture of the corpus cavernosum from blunt trauma to the erect penis (3,4). Typical presentation is a pop during intercourse, immediate detumescence with edema, hematoma and penile deformity (3,4). In atypical presentations, radiological studies may be useful to determine the diagnosis. MRI provides the ability to identify disruption of the corpus cavernosum due to excellent tissue contrast and Penile Fracture and Magnetic Resonance Imaging _______________________________________________

To determine the association of MRI features of extra-abdominal desmoid tumours (DTs) with prognosis. MRIs for 90 patients with DT were retrospectively reviewed for imaging features associated with biological behaviour. The primary end point was progression (for lesions managed with chemotherapy, radiation therapy and observation) or recurrence (following surgery). Time to event was studied using univariate and multivariable Cox proportional hazards regression models when accounting for demographic, clinicopathological and imaging variables. Kaplan-Meier plots were used to estimate event-free rate (EFR). Univariate analysis revealed a significant relationship between EFR and treatment, location and compartment of origin [subcutaneous (SC), superficial fascial, intramuscular (IM) and deep fascial/intermuscular]. None of the imaging features commonly associated with biological behaviour of DTs (e.g., shape, enhancement, T2 signal etc.) or surgical margins (in surgical cases) was associated with EFR. Multivariate analysis showed that treatment modality and compartment of origin were independent predictors of EFR. Superficial and deep fascial lesions had a significantly worse EFR as a group [hazard ratio: 3.9; 95% confidence interval (CI): 1.83-8.32; p = 0.0004] than did the SC and IM lesions as a group. 5-year EFR for the fascial lesions was 18% (95% CI: 6-36%), compared with 57% (95% CI: 25-79%) for the SC and IM groups. Intramuscular or SC DTs may be associated with improved prognosis. If validated on multireader and prospective studies, these results can provide for rapid risk stratification at the time of initial MRI. This work has shown that imaging features commonly associated with biological activity of desmoid tumours (e.g. shape, T2 signal and enhancement) do not appear to be associated with prognosis in patients undergoing a variety of treatment modalities. The compartment of origin of the lesion, which can be determined on pre-operative MRI, was shown to be associated with prognosis and can allow for risk stratification in patients with DTs.

Desmoid Tumor of the Rectus Abdominis Muscle in a Postpartum Patient

Desmoid Tumor Following Augmentation Mammoplasty with Silicone Implants

Extra-adrenal myelolipoma and extramedullary hematopoiesis: Imaging features of two similar benign fat-containing presacral masses that may mimic liposarcoma

PII: S0344-0338(89)80172-4

The purpose of this study was to investigate the ability of MR imaging to show desmoid tumors in patients with familial adenomatous polyposis, to document the appearances of these tumors, and to identify possible predictors of growth. CT and MR imaging of 15 patients with familial adenomatous polyposis and known abdominal wall or intraabdominal desmoid tumors were performed. Nine patients underwent follow-up CT and MR imaging, and four patients had undergone CT within the previous 12 months. Unenhanced and gadolinium-enhanced T1-weighted MR imaging sequences and T2-weighted MR imaging sequences were performed, as was unenhanced and IV contrast-enhanced helical CT. The CT and MR images were independently assessed. CT revealed 35 desmoid tumors: 22 were intraabdominal and 13 were in the abdominal wall. MR imaging revealed 21 of the 22 intraabdominal desmoid tumors and 13 of the 13 abdominal wall desmoid tumors. MR imaging and CT findings agreed precisely on the site and margin of the intraabdominal and abdominal wall desmoid tumors. CT was more effective in revealing their relationship to the bowel. Contrast enhancement was more easily identified on MR images than on CT scans, especially when enhancement was inhomogeneous. High signal intensity on T2-weighted images was seen in eight desmoid tumors, all of which showed significant growth on follow-up scans. MR imaging can show both intraabdominal and abdominal wall desmoid tumors in patients with familial adenomatous polyposis. High signal intensity on T2-weighted images was seen from desmoid tumors that had shown marked growth on follow-up imaging.

To analyze the appearance of primary and recurrent aggressive fibromatosis (AF) on MRI with a focus on configuration and to determine potential risk factors for recurrences detected on MRI follow-up scans. From 79 consecutive patients with histologically proven diagnosis of AF, 39 patients underwent a minimum of four 1.5 T MRI follow-up scans after resection of primary AF between 2008 and 2018. The primary and recurrent tumors were radiographically examined for configuration, limitation and extent on MRI. Epidemiological data and loco-regional subcutaneous edema, muscle edema and post-operative seroma were included. The mean age of the patients was 39 ± 2.6 years. Primary and recurrent AF most often occurred in the thigh. The main appearance of primary AF was significantly most often fascicular (p = 0.001-0.01) with heterogeneous and marked contrast enhancement. 21 % (n = 8) of the patients developed recurrences of AF. A fascicular configuration with homogeneous/heterogeneous contrast enhancement was the main appearance of recurrent AF, but recurrent AF appeared nodular, polycyclic, ovoid or streaky/flat as well. Recurrent AF significantly most often occurred within the first 9 months after primary tumor resection (p = 0.009), especially in patients up to 25 years of age (RR = 6.1; 95 % CI: 1.8-20.9; p = 0.004). The cases of recurrent AF were altogether significantly smaller than the primary tumors (p = 0.001). Post-treatment subcutaneous and muscle edema were present in 77 % and 56 %, respectively. Patients with muscle edema after primary tumor resection had a significantly higher risk for AF recurrences (relative risk ratio (RR) = 1.8; 95 % CI: 1.16-2.8; p = 0.0096). There was no significant difference detected in patients with complete or incomplete resection of the primary tumor. Primary and recurrent aggressive fibromatosis has a mostly fascicular configuration, but may appear ovoid, nodular, streaky/flat or polycyclic as well. High risks for tumor recurrences are detected for patients up to 25 years of age, patients within the first 9 post-operative months and patients with muscle edema after primary tumor resection. · Primary aggressive fibromatosis mostly has a fascicular configuration with heterogeneous contrast enhancement. · Recurrent aggressive fibromatosis usually has a fascicular configuration with heterogeneous/homogeneous contrast enhancement. · Patients within the first 9 post-operative months and up to 25 years of age have a significantly higher risk for recurrences. · Muscle edema after resection of primary aggressive fibromatosis is associated with a significantly higher risk for recurrences. · Sedaghat S, Surov A, Krohn S et al. Configuration of Primary and Recurrent Aggressive Fibromatosis on Contrast-Enhanced MRI with an Evaluation of Potential Risk Factors for Recurrences in MRI Follow-Up. Fortschr Röntgenstr 2020; 192: 448 - 457.

11515 Background: For patients with desmoid tumors (DT, aggressive fibromatosis), systemic therapy that results in tumor regression, symptom improvement and durable tolerability is needed. Gamma secretase inhibitors (GSIs) have demonstrated antitumor activity against DT. AL102 is a potent, orally available, selective GSI under investigation for treatment of DT. Methods: RINGSIDE (AL-DES-01) is a Phase 2/3 study for patients with progressing DT. In the open-label Phase 2 study (Part A), adults with progressing DT (≥10% unidimensional growth within 18 months or DT-related pain requiring non-opioid medication) were randomized to three dosing regimens: 1.2 mg QD, 2 mg intermittent BIW (2 days on 5 days off), or 4 mg intermittent BIW. Patients who complete Phase 2 roll over into an open-label extension (OLE). RINGSIDE Phase 3 (Part B) is a double-blind, placebo-controlled study evaluating the chosen dose regimen from Phase 2 (1.2 mg once daily) utilizing PFS as the primary endpoint. We report updated efficacy and safety results from RINGSIDE Phase 2. Results: Enrollment of all 42 patients into Phase 2 was completed as of March 2022. As of January 3, 2023, median time on study was 10.5 months (range 0.8 – 14.7) and 30 patients (71.4%) were still on study, 10 (23.8%) of whom rolled over to the OLE. Mean age was 39.9 years, 73.8% were women and 69% had received prior desmoid cancer therapy. The best response in the evaluable population as assessed by blinded independent central review (BICR) was partial response (PR) in 6/12 patients (50%) for 1.2 mg QD, 3/13 patients (23.1%) for 4 mg BIW, and 5/11 patients (45.5%) for 2 mg BIW. Disease control rate was 100%, 91%, and 97% in these groups, respectively. A consistent pattern of deeper, more rapid and maintained response was observed with 1.2 mg QD. Median volume change (BICR) from baseline was -51.9% for 1.2 mg QD, -9.5% for 4 mg BIW, and -15.2% for 2 mg BIW at Week 16 and -76.4%, -35.5%, and -51.2%, respectively, at Week 28. Similar patterns were observed for % changes from baseline in T2 signal intensity, suggesting reduction of tumor cellularity. Consistent with the mechanism of action of GSIs, the five most common Grade 1-2 treatment-emergent adverse events (TEAEs) were diarrhea, nausea, fatigue, alopecia, and dry skin. Grade 3 drug-related TEAEs were reported in 26.2% of patients across all tested doses. There were no Grade 4, Grade 5, or serious TEAEs related to AL102 per investigator assessment. There were no new safety signals. Conclusions: In this Phase 2 study, AL102 was safe and generally well tolerated across all tested doses. The safety profile was consistent with the GSI class of drugs. Tumor response, volume reduction and T2 signal reduction were observed earlier in the 1.2 mg QD group, with deeper and maintained treatment responses. This dose was selected for study in RINGSIDE Phase 3, which is currently enrolling in multiple countries. Clinical trial information: NCT04871282 .

Signet Ring Rectal Cancer (SRRC) of rectum is rare high-grade subtype with poor prognosis and characteristic histopathology. We evaluated its imaging appearance and correlated its outcomes. We conducted a retrospective review of the rectal MRIs of 97 patients with rectal SRRC, evaluating tumor morphology, T2 signal, length, location, pattern of tumor growth, nodal status and location, EMVI (extramural vascular invasion), site of metastases, and response to chemotherapy. The tumor signal on T2W images was categorized into intermediate, T2 hyperintense, and fluid/mucin bright. Imaging findings were correlated with risk of metastatic/ recurrent disease, disease-free survival, and overall survival. The median age of patients of SRRC in our study was 35years and more frequently found in male patients. The common imaging features of SRRC were T2-hyperintense signal (63%), infiltrative growth pattern (76%), positive MR CRM (Circumferential Resection Margin on MRI) (84%), presence of EMVI (51%), and advanced T and N stage (97% and 84%, respectively). Peritoneum and nodes were the most common sites of metastases. Raised serum CEA (Carcino-embryonic Antigen) levels, positive MR CRM status, extramesorectal adenopathy, and advanced N stage had statistically significant predictive value for recurrence or metastases. Elevated serum CEA levels (p = 0.019) and intermediate T2 signal (p = 0.012) demonstrated significant independent association with poor overall survival, while advanced N stage (p = 0.033) demonstrated significant independent association with worse disease-free survival in multivariate analysis. SRRC affected young patients and demonstrated T2-hyperintense signal and subepithelial spread in an infiltrative pattern. Elevated CEA levels and T2-intermediate signal intensity are independent predictors for worse overall survival and advanced nodal stage is independent prognostic factor of poor disease-free survival. MRI rectum can pinpoint the pathology given the distinct MRI morphology and age of presentation.

ObjectivesBecause size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity.MethodsThis IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters.ResultsMedian patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 - 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 - 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 - 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p<0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12).ConclusionsAnalysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability.

Background: Desmoid tumors (DT) are rare fibroblastic sarcomas that have high recurrence rates. Though we know mutations in the beta-catenin (CTNNB1) gene are commonly observed with dysregulation of the Wnt signaling pathway in patients with DT, the molecular mechanisms driving DT growth remain poorly understood. There is currently no standard systemic treatment for DT. The multi-kinase inhibitor, sorafenib, has been identified as a potential front-line agent for DT after a recent clinical trial demonstrated an objective response in one third of patients. The mechanism for how sorafenib inhibits DT progression is still unclear, so it is unknown which characteristics predict response to the drug. Our work has identified the early growth response-1 (EGR1) gene as a downstream target of sorafenib. Methods: Nine DT cell lines have previously been brought into culture with stable passage. These cell lines were treated with sorafenib at 10 μM. RNA was collected from parental and treated cells and subsequent RNA sequencing was performed. Differential gene expression was performed using R. Appropriate comparisons for multiplicity were performed. Western blots were performed to confirm changes in expression of key genes at the protein level. EGR1 overexpression vector was introduced to the 2 DT cell lines and further treated with sorafenib. Additional banked patient desmoid tumor samples were sequenced to assess EGR1 levels and correlation with the CTNNB1. Results: We first evaluated the effect of sorafenib on CTNNB1 in the DT models. Western blot demonstrated no changes in protein levels of CTNNB1 in the 4 cell lines tested at 72 hours post-treatment. This was further confirmed on RNA-sequencing. To identify additional gene targets of sorafenib, additional differential gene expression analysis was performed resulting in 13 altered genes at an adjusted p &amp;lt; 0.01. The most significantly altered gene, both by p-value and by fold change, was the EGR1 mRNA transcript. EGR1 transcript levels were significantly attenuated by sorafenib treatment (logFC = 2.720, adjusted p-value &amp;lt;&amp;lt; 0.0001). Western blot analysis confirmed this decrease. EGR1-high DT cell line models exhibited faster growth rates and also higher sensitivity to sorafenib. Fifteen additional patient desmoid tumor samples confirmed the steady state of CTNNB1 and high variability of the EGR1 transcript. There was no correlation between the EGR1 and CTNNB1 transcript. Conclusion: This study found that sorafenib does not directly modulate CTNNB1, but does decrease EGR1 expression at both the mRNA and protein level. This suggests that EGR1 expression may be associated with aggressive DT and may also predict responsiveness to treatment with sorafenib. Confirmatory EGR1 modulation experiments are underway and will be provided at time of presentation. Citation Format: Max Devine, Joy Tang, Colin Stets, John Hays, James L. Chen. Characterizing the molecular underpinnings of sorafenib sensitivity in desmoid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2777.