Median Lesion Research Articles

Imaging Patterns of Bacillus Calmette–Guérin-Related Granulomatous Prostatitis Based on Multiparametric MRI

ObjectiveTo categorize multiparametric MRI features of Bacillus Calmette–Guérin (BCG)-related granulomatous prostatitis (GP) and discover potential manifestations for its differential diagnosis from prostate cancerMaterials and MethodsThe cases of BCG-related GP in 24 male (mean age ± standard deviation, 66.0 ± 9.4 years; range, 50–88 years) pathologically confirmed between January 2011 and April 2019 were retrospectively reviewed. All patients underwent intravesical BCG therapy followed by a MRI scan. Additional follow-up MRI scans, including diffusion-weighted imaging (DWI), were performed in 19 patients. The BCG-related GP cases were categorized into three: A, B, or C. The lesions with diffusion restriction and homogeneous enhancement were classified as type A. The lesions with diffusion restriction and a poorly enhancing component were classified as type B. A low signal intensity on high b-value DWI (b = 1000 s/mm2) was considered characteristic of type C. Two radiologists independently interpreted the MRI scans before making a consensus about the types.ResultsThe median lesion size was 22 mm with the interquartile range (IQR) of 18–26 mm as measured using the initial MRI scans. The lesion types were A, B, and C in 7, 15, and 2 patients, respectively. Cohen’s kappa value for the inter-reader agreement for the interpretation of the lesion types was 0.837. On the last follow-up MRI scans of 19 patients, the size decreased (median, 5.8 mm; IQR, 3.4–8.5 mm), and the type changed from A or B to C in 11 patients. The lesions resolved in four patients. In five patients who underwent prostatectomy, caseous necrosis on histopathology matched with the non-enhancing components of type B lesions and the entire type C lesions.ConclusionBCG-related GP demonstrated three imaging patterns on multiparametric MRI. Contrast-enhanced T1-weighted imaging and DWI may play a role in its differential diagnosis from prostate cancer.

Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis

BackgroundMultiple Sclerosis (MS) lesions are pathologically heterogeneous and the temporal behavior in terms of growth and myelination status of individual lesions is highly variable, especially in the early phase of the disease. Thus, monitoring the development of individual lesion myelination by using quantitative magnetic resonance myelin water imaging (MWI) could be valuable to capture the variability of disease pathology and get an individual insight into the subclinical disease activity. ObjectiveThe goal of this work was (1) to observe the variation and longitudinal change of in vivo lesion myelination by means of MWI and its parameter Myelin Water Fraction (MWF), and, (2) to identify individual lesion myelination patterns in early MS. MethodsIn this study n = 12 patients obtained conventional MRI and quantitative MWI derived from multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) within four weeks after presenting a clinically isolated syndrome and remained within the study if clinically definitive MS was diagnosed within the 12 months study period. Four MRI sessions were acquired at baseline, 3, 6, and 12 months. The short-term and long-term variability of MWF maps was evaluated by scan-rescan measures and the coefficient of variation was determined in four healthy controls. Tracking of individual lesions was performed using the Automatic Follow-up of Individual Lesions (AFIL) algorithm. Lesion volume and MWF were evaluated for every individual lesion in all patients. Median lesion MWF change was used to define lesion categories as decreasing, varying, increasing and invariant for MWF variation. ResultsIn total n = 386 T2 lesions were detected with a subset of n = 225 permanent lesions present at all four time-points. Among those, a heterogeneous lesion MWF reduction was found, with the majority of lesions bearing only mild MWF reduction, approximately a third with an intermediate MWF decrease and highest MWF reduction in acute-inflammatory active lesions. A moderate negative correlation was determined between individual lesion volumes and median MWF consistent across all time-points. Permanent lesions featured variable temporal dynamics with the majority of varying MWF (58 %), however decreasing (16 %), increasing (15 %) and invariant (11 %) subgroups could be identified resembling demyelinating activity and post-demyelinating inactivity known from histopathology studies. Inflammatory-active enhancing lesions showed a distinct pattern of MWF reduction followed by partial recovery after 3 months. This was similar in new enhancing lesions and those with a non-enhancing precursor lesion. ConclusionThis work provides in vivo evidence for an individual evolution of early demyelinated MS lesions measured by means of MWF imaging. Our results support the hypothesis, that MS lesions undergo multiple demyelination and remyelination episodes in the early acute phase. The in vivo MRI surrogate of myelin turnover bears capacity as a novel biomarker to select and potentially monitor personalized MS treatment.

Diffusion Restricted Lesions in the Splenium of the Corpus Callosum.

Various neurological disorders are associated with lesions predominantly or exclusively affecting the splenium of the corpus callosum (CC), such as Marchiafava-Bignami syndrome (MBS), reversible splenium lesion (RSL), and ischemic stroke (IS). The spectrum of symptoms is broad and clinical presentations may be indistinguishable. Therefore, we aimed to investigate the additional value of diffusion-weighted imaging (DWI) findings of splenial lesions in patients with MBS, RSL, and IS. Overall, 23 patients (4 patients with MBS, 10 patients with RSL, and 9 patients with isolated IS in the splenium) were identified from a magnetic resonance imaging report database and analyzed with focus on lesion localization, shape, and size on DWI, as well as relative apparent diffusion coefficient (ADC). A focal hyperintensity in the splenium was observed on DWI in all patients. In MBS symmetrical boomerang-shaped lesions, in RSL central oval or round lesions, and in IS eccentric irregular lesions in the splenium were found. The median lesion size in MBS [6.25 (IQR=2.04-8.62) ml] was significantly larger than that in RSL [0.38 (IQR=0.09-0.92) ml, p=0.01], and in IS [0.09 (IQR=0.05-0.94) ml; p=0.01]. Regarding relative ADC values, no significant differences between MBS [0.32 (IQR=0.19-0.62)], RSL [0.22 (IQR=0.14-0.30)], and IS [0.27 (IQR=0.20-1.19)] were found. Diffusion restricted lesions in the splenium of the CC are best classified by localization, shape, and size, whereas relative ADC values are of limited value for differentiation of different neurological disorders.

First Experience With The GoBack-Catheter For Successful Crossing of Complex Chronic Total Occlusions in Lower Limb Arteries

Purpose: To evaluate the use of the GoBack-catheter (Upstream Peripheral Technologies) in complex revascularizations in lower limb arteries. Materials and Methods: In this retrospective single-center study, the results of the first 100 consecutive patients including 101 limb-revascularizations, performed between May 2018 and July 2020 with the study device, were analyzed. In all cases, guidewire-crossing failed, and all lesions were chronic total occlusions (CTO), either de novo, reocclusions, or in-stent reocclusions. Successful crossing was defined as passing the CTO using the study device. Patency at discharge and after 30 days was defined as less than 50% restenosis on duplex sonography, without target lesion revascularization. Results: Median lesion length was 24 cm and 38 patients (37.6%) had a calcium grading according to the peripheral arterial calcium scoring system (PACSS) of 4 or 5. In 20.8% of patients, an occluded stent was treated. CTOs involved the femoropopliteal segment in 91.1%, iliac arteries in 5.9%, and tibial arteries in 7.9%. The GoBack-catheter was employed for entering into or crossing through parts or the full length of a CTO or an occluded stent as well as for re-entering into the true lumen after subintimal crossing. The device was used via contralateral and ipsilateral antegrade as well as retrograde access with an overall technical success rate of 92.1%. In 3 patients minor bleeding occurred at the crossing or re-entry site, which were managed conservatively. Thirty-day adverse limb events comprised minor amputations in 4 patients (4.0%), 1 major amputation (1.0%), and reocclusions in 7 limbs (6.9%). Conclusion: The new GoBack-catheter offers versatile endovascular applicability for complex CTO recanalization in a broad range of peripheral vascular interventions with a high technical success and low complication rate.

Single operator experience of endoscopic submucosal dissection for Barrett's neoplasia in a North American academic center.

ObjectivesEndoscopic submucosal dissection (ESD) is carving out an increasing role in the treatment of Barrett's associated neoplasia. ESD provides the advantage of en‐bloc resections and greater R0 resection rates. We aim to present outcomes from one of the largest single‐center cohorts of esophageal ESD in North America.MethodsAll patients undergoing esophageal ESD for Barrett's neoplasia between Oct 2016 and June 2020 at a Canadian tertiary care center were included. Demographic, procedural data, and lesion characteristics are presented. Subgroup analysis was performed on patients who underwent extensive resection (≥75% of esophageal circumference) and the patients who developed strictures.ResultsThirty‐four patients were included in the series. The median lesion diameter was 5.7 cm and the median procedure time was 129 min. The en‐bloc resection rate was 97%, and the R0 resection rate was 91%. Curative resection was achieved in 82% of patients. Upstaging in histology occurred in 59% of cases. Two adverse events occurred, and there were no perforations. Procedural outcomes were similar in patients with extensive resections, but those with ≥75% circumferential resection developed more strictures (65% vs. 6.3%, p < 0.01). Stricture formation was associated with extensive resection (odds ratio [OR]: 27.5, p < 0.01) and longer lesion diameter (OR: 1.7, p = 0.02).ConclusionOur experience with ESD for Barrett's related neoplasia shows excellent en‐bloc and R0 resection rate, and provides more accurate histological specimens. Curative resection is possible in the majority of cases, including those with extensive resections. Further investigation into stricture prophylaxis will be useful as near circumferential resections are attempted.

Endoscopic transcecal appendectomy: a new endotherapy for appendiceal orifice lesions.

Background Endoscopic transcecal appendectomy (ETA) has been reported as a minimally invasive alternative procedure for lesions involving the appendiceal orifice. The aim of this case series study was to evaluate the feasibility, safety, and effectiveness of ETA for lesions at the appendiceal orifice. Methods This retrospective study included consecutive patients with appendiceal orifice lesions who underwent ETA between December 2018 and March 2021. The primary outcome was technical success. The secondary outcomes included postoperative adverse events, postoperative hospital stay, and recurrence. Results 13 patients with appendiceal orifice lesions underwent ETA during the study period. The median lesion size was 20 mm (range 8–50). Lesions morphologies were polypoid lesions (n = 5), laterally spreading tumors (n = 4), and submucosal lesions (n = 4). Technical success with complete resection was achieved in all 13 cases. There were no postoperative bleeding, perforation, or intra-abdominal abscess. The median length of hospital stay after ETA was 8 days (range 6–18). There was no tumor recurrence during a median follow-up of 17 months (range 1–28). Conclusions ETA is feasible, safe, and effective for complete resection of appendiceal orifice lesions. Larger, multicenter, prospective studies are needed to further assess this technique.

Incremental benefit of dye-based chromoendoscopy to predict the risk of submucosal invasive cancer in large nonpedunculated colorectal polyps

Detailed lesion assessment of large nonpedunculated colorectal polyps (LNPCPs;≥20mm) can help predict the risk of submucosal invasive cancer (SMIC). Traditionally this has required the use of dye-based chromoendoscopy (DBC). We sought to assess the accuracy and incremental benefit of DBC in addition to high-definition white-light imaging (HDWLI) and virtual chromoendoscopy (VCE) for the prediction of SMIC within LNPCPs. A prospective observational study of consecutive LNPCPs at a single tertiary referral center was performed. Before resection all lesions were assessed for the presence of a demarcated area (DA), defined as an area of disordered pit or microvascular pattern, by 2 trained endoscopists before and after DBC. Diagnostic performance characteristics were calculated with histology as the reference criterion standard, and overall agreement was calculated using the κ statistic. Over 39 months to March 2021, 400 consecutive LNPCPs (median lesion size, 35mm; interquartile range, 25-45) were analyzed. The overall rate of SMIC was 6.5%. Presence of a DA had an accuracy of 91% (95% confidence interval, 87.7-93.5) for SMIC, independent of the use of DBC. The rate of interobserver agreement for presence of a DA using HDWLI+ VCE was very high (κ= .96) with no benefit gained by the addition of DBC. The use of HDWLI and VCE is likely to be adequate for lesion assessment for the prediction of SMIC among LNPCPs. Further, the absence of a DA is strongly predictive for the absence of SMIC, independent to the use of DBC. (Clinical trial registration number: NCT03506321.).

An open-label prospective study to assess short incubation time white LED light photodynamic therapy in the treatment of superficial basal cell carcinoma.

Artificial white LED light photodynamic therapy (awl-PDT) is an effective, pain-free treatment for actinic keratosis. The efficacy of awl-PDT in the treatment of superficial basal cell carcinoma (sBCC) has not been assessed. Patients with histologically confirmed sBCC underwent two treatments of awl-PDT 1week apart. Lesions were incubated with methyl 5-aminolaevulinic acid for 30min and then illuminated using the Maquet Power LED 500 theatre light (405-800nm, 140000 lux) to deliver an equivalent red light dose of 75J/cm2 at a rate of 55mW/cm2 . Pain was measured using a visual analogue scale during treatment. Clinical response was assessed at day 28. Follow-up continued 3months for 1year. Cosmetic outcome was assessed at 3months and 1year. Twenty-eight patients with 36 lesions and a mean age of 63.64 (SD 2.62) were recruited. The median lesion size was 15mm (IQR 8.75). The response rate at day 28 was 100%. Recurrence rates were 3/36 (8.3%) at 3months, 6/36 (16.7%) at 6months, 10/36 (27.8%) at 9months and 11/36 (30.6%) at 1year. Median pain scores were 0/100 (IQR 0) and 0/100 (IQR 5) during treatments one and two, respectively. Cosmetic outcome was excellent or good in the majority of cases. Although initially effective for sBCC at 28days, 30.6% of lesions recurred 1year after awl-PDT. Pain scores were negligible, and the cosmetic outcome was favourable. Further head-to-head studies with optimised protocols are required to determine if awl-PDT has a role in the treatment of sBCC.

Quantification of Tc-99m macroaggregated albumin liver perfusion as a predictor of tumor response to intra-arterial therapy with yttrium 90 spheres

Objectives: It remains unclear whether quantifying the pre-therapy tumor Technetium 99m macro aggregated albumin (Tc 99m MAA) localization can accurately predict the response to Yttrium 90 (Y-90) spheres therapy. Present studies are limited and with contradictory results. The aim of this study is to determine if quantification of Tc-99m MAA in hepatic tumor lesion(s) on pretherapy planning nuclear scan can predict the degree of tumor response after radioembolization using Y-90 Spheres. Material and Methods: We retrospectively included patients with primary liver cancers or metastases who were treated with SirSpheres or TheraSpheres. All patients had a Tc-99m MAA scan with an average dose of 5.0mCi injected aseptically in either the right, left, or common hepatic artery. The patients were subsequently transferred for imaging using planar and single-photon emission computed tomography (SPECT) of the abdomen and planar images of the chest. We calculated geometric mean of radiotracer counts in the largest lesion in the lobe to be treated by placing same size region of interest (ROI) around the largest lesion on the anterior and posterior planar images. Subsequently, an irregular ROI around the liver or lobe to be treated were drawn to calculate the geometric mean of counts in the liver. The percent tracer accumulation in the largest lesion was calculated by dividing the geometric mean of counts in the largest lesion by the geometric mean of counts in the liver or lobe and multiplying by 100%. The size of this largest lesion was obtained on the most recent CT or magnetic resonance imaging (MRI) in cm in 2 directions prior to treatment with Y-90 Spheres. The extent of the response to Y-90 Spheres therapy was re-evaluated with 3 months follow-up MRI or CT by measuring the decrease in the largest lesion size. Comparison of the percent Tc-99 MAA count accumulation in the largest lesion on the pre-therapy scan with the reduction in size using anatomic imaging was performed. Results: A total of 30 patients were included (16 hepatocellular carcinoma, eight colorectal, three breast, one neuroendocrine, one cholangiocarcinoma, and one cervical metastases). There were 14 patients in stable disease or progressive disease group (SD/PD gp) and 16 patients in partial response or complete response group (PR/CR gp). The median lesion size was 3.5 cm in the PD/SD gp versus 2.8 cm in the PR/CR gp (P = 0.31). Additionally, the median delivered Y90 Spheres treatment dose was 51.3 mCi in the PD/SD versus 43.2 mCi in the PR/CR gp (P = 0.22). The percent median largest lesion to liver concentration was 21.9% in the PR/CR gp versus 23.3% in the PR/CR gp (P = 0.74). There was no significant difference in percent Tc-99m MAA distribution in the largest liver lesion between the SD/PD gp and the PR/CR gp. Conclusion: The degree of Tc-99m MAA localization in the largest tumor lesion in the liver compared to the remainder of the liver as quantified from planar images does not predict the response to Y-90 spheres therapy.

Arterial Preparation by Longitudinal Micro-Incisions Before Balloon Angioplasty of the Superficial Femoral and Popliteal Artery: Acute and 12-Month Results

Purpose: Percutaneous transluminal angioplasty (PTA) with conventional plain old balloon (POBA) and/or drug-coated balloon (DCB) is the primary intervention to treat peripheral artery stenoses. However, acute dissections during the procedure and potential for future target lesion revascularization remain procedural complications. The purpose of this study was to assess the acute and 12-month outcomes in patients who underwent novel vessel preparation with longitudinal, controlled-depth micro-incisions prior to PTA. Materials and Methods: Patients with symptomatic lower extremity peripheral arterial disease with a Rutherford class of 2 to 6 and >70% de novo stenosis of the superficial femoral or popliteal arteries were included in this retrospective study. Patients with thrombotic or embolic lesions, restenosis, or in-stent restenosis were excluded. The FLEX Vessel Prep System (FLEX VP) was used to prepare the vessel prior to PTA by creating micro-incisions at the target lesion. The FLEX VP was followed by POBA or paclitaxel DCB. Results: The study included 65 patients. Lesion characteristics were 90% median stenosis (range = 70%–100%), 75.4% mild-to-severe calcifications, and 33.8% occlusion rate, and median lesion length was 196 (range = 10–480) mm. Following vessel preparation, 82.1% of the patients had low severity dissection or no flow-limiting dissection. The provisional stent rate postprocedure was 16.9%, with a median stent length of 60 mm. The freedom from target lesion revascularization (FFTLR) in 63 evaluable patients at 6 and 12 months was 98.4% and 93.7%, respectively. Freedom from amputation was 100%. Conclusion: In this real-world/all-comers patient population with long, stenotic lesions across the calcification spectrum, vessel preparation with longitudinal micro-incisions prior to PTA was associated with low dissection rate, low dissection severity, low stent implantation, and high FFTLR with the absence of amputation at 12 months relative to published reports in long-lesion cohorts. These results support vessel preparation via micro-incisions.

Lesion Characteristics and Patterns of Failure in Diffuse Large B Cell Lymphoma Patients Treated with Bridging Radiotherapy Prior to Chimeric Antigen Receptor T Cell Therapy

Lesion Characteristics and Patterns of Failure in Diffuse Large B Cell Lymphoma Patients Treated with Bridging Radiotherapy Prior to Chimeric Antigen Receptor T Cell Therapy

A Multicenter Large Retrospective Database on the Personalization of Stereotactic Ablative Radiotherapy for Lung Metastases From Colon-Rectal Cancer: The LaIT-SABR Study

<h3>Purpose/Objective(s)</h3> stereotactic ablative radiotherapy (SABR) has been shown to increase survival rates in oligometastatic disease (OMD), but local control of colorectal metastases still remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate how lung SBRT can impact on the progression to the polymetastatic disease (PMD). <h3>Materials/Methods</h3> the study involved 22 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1023 lung metastases treated with SBRT in 622 patients were reported. The median BED was 105 Gy¹⁰. Lesion diameter GTV, PTV volume, dose, fractionations, and site of primary tumor were evaluated as potential predictive marker for SBRT response for the primary end-point local progression-free survival (LPFS). EGFR, KRAS, NRAS, BRAF, and MSI were also evaluated. Secondary end-point was the time to the polymetastatic conversion (ttPMC). <h3>Results</h3> the median follow-up was 26 months (range 3-117 months). The median lesion diameter was 13 mm (range 4-58 mm). The 2- and 3-year LPFS were 75.6% and 71%, respectively. At the univariate analysis, BED ≥125Gy¹⁰ was associated with improved LPFS (2-year: 94.1% versus 72.6%; <i>P</i> = < 0.0001), single fraction SBRT correlated with better LPFS in the overall population (2-year: 80.6% versus 73.7%; <i>P</i> = 0.03), but no significant difference was observed when considering the population treated with BED > 100 Gy¹⁰. Lesion diameter ≤19 mm correlated with improved LPFS (2-year 80% versus 60%; <i>P</i> = < 0.0001). The median ttPMC was 26 months, and the 2-year ttPMC was 54.5%. The median PFS was 11.3 months. After SABR, 36% patients had polymetastatic relapse, 39.5% patients had an oligometastatic relapse, and 24.5% patients had no further relapse. <h3>Conclusion</h3> the present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Several biological and clinical predictive factors were identified to assure the highest local control, on the basis of which a decisional algorithm will be derived.

Toxicity and Dosimetric Parameters of Ablative Radiation Therapy in the Management of Patients with Child-Pugh B/C Liver Function and Unresectable Hepatocellular Carcinoma (HCC)

To date there is no clear standard non-surgical therapeutic option for HCC patients. Ablative radiation therapy (SBRT/HIGRT) is an emerging non-invasive treatment for patients with HCC. However, there is concern about the risk for radiation-induced liver toxicity following radiation in patients with decompensated liver function (Child-Pugh B/C).We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT and underlying Child-Pugh B or C liver function prior to radiation therapy at our University and Veterans Affairs (VA) radiation oncology departments from 2014 to 2019. Primary endpoints included treatment-related toxicity, as well as, evaluation of dosimetric parameters for OAR.38 patients (39 treatment courses) were included. Most patients (97%) had Child-Pugh B7-B9 (62% CP B7, 21% CP B8, 15% CP B9) or ALBI grade 2-3 (69% ALBI grade 2, 31% ALBI grade 3) liver disease prior to radiation therapy. A single patient had Child-Pugh C10 liver function. The most commonly utilized regimens include 50 Gy in either 5 or 10 fractions. The median delivered dose was 50 Gy (range 30-50) in an average of 7.5 fractions (range 5-10). Most patients had a single lesion (63%) with a median lesion size of 3.2 cm (range 1.10-7.40 cm). The mean liver dose was 9.40 Gy (range 3.38-23.94) with a liver D800cc of 4.14 Gy (range 0.35-17.31). All patients completed their intended treatment course with a median follow up of 43 months. Four (10.3%) treatment courses resulted in non-classical radiation-induced liver disease (RILD) (defined as an increase of 2 or more points in Child-Pugh score), compared to 8.3% for patients with Child-Pugh A liver function treated during a similar time period. Otherwise, one patient (2.6%) experienced acute grade 3+ (non-RILD) hepatobiliary toxicity (transient transaminitis). Two-year freedom from local progression was 73% (95% CI 37-90%), median overall survival 12 months (95% CI 5-25 months), and median progression free-survival was not reached.Ablative radiation therapy as definitive management for patients with unresectable, non-metastatic HCC appears to be reasonably well tolerated in patients with decompensated liver function at baseline (Child-Pugh B7-B9), with low rates of RILD and encouraging local control. With careful selection, these patients appear to be reasonable candidates for consideration of SBRT/HIGRT. Our analysis did not include enough patients with Child-Pugh C10+ disease to draw meaningful conclusions.

Stereotactic Body Radiation Therapy and Immunotherapy in Abdominal and Pelvic Lymph Node Metastases

This study characterizes the efficacy and safety of stereotactic body radiation therapy (SBRT) with immunotherapy in the treatment of abdominal and pelvic lymph node metastases, based on a pooled analysis of three prospective phase I trials. While SBRT is frequently utilized for metastases, its role in the treatment of abdominal and pelvic lymphadenopathy remains unclear. We hypothesize that local control will remain excellent for nodal SBRT, even with prioritization of organ-at-risk (OAR) constraints resulting in undercoverage of target metastases and with omission of elective treatment of regional nodal basins.Patients with widely metastatic solid malignancies were enrolled on three Phase I trials between 2016 and 2020 (total 213 patients). Patients were treated with multisite SBRT (up to 4 sites). Metastases > 65cc were partially treated. Immunotherapy was administered either concurrently or sequentially. Immunotherapy regimens included pembrolizumab, ipilimumab with nivolumab, urelumab with nivolumab, or cabiralizumab with nivolumab. The study cohort included patients who underwent SBRT to at least one lymph node in the abdomen or pelvis, including the inguinal regions. Local control (LC) of irradiated metastases and regional control (RC) of the corresponding nodal basin were determined per RECIST 1.1 guidelines. Overall survival (OS) was calculated using the Kaplan-Meier method. For each irradiated lesion, the mean dose, V95%, and V100% to the ITV and PTV were recorded.A total of 39 patients (mean age 59.2 years) underwent SBRT to 56 abdominal or pelvic lymph node metastases with median follow-up of 16.2 months. The median prescription dose was 45 Gy in 3 fractions. Median lesion volume was 17.0cc. Lymph node sites included 24 para-aortic/retroperitoneal (43%), 9 pelvic (16%), 11 inguinal (20%), 10 gastrohepatic/porta hepatis (18%), and 2 other (4%). Across all patients, the 1-year LC was 90.4%. Even without elective treatment of the corresponding nodal basins, 1-year RC was 81.9% (with only one isolated regional failure without concomitant distant progression). Median OS was 25 months, while 1-year and 2-year OS were 69.9% and 53.2%, respectively. ITV mean dose, V95%, and V100% were 47.3 Gy, 95.3%, and 89.5%, respectively (reported as medians across all 56 metastases). PTV mean dose, V95%, and V100% were 45.5 Gy, 84.2%, and 75.0%, respectively. The overall incidence of grade 3+ toxicity was 10.3%. The incidence of grade 3 colitis was 2.6% and grade 3 hepatitis was 2.6%, with no grade 4-5 colitis/hepatitis events.In this pooled analysis of three prospective trials, SBRT to abdominal or pelvic lymph node metastases with immunotherapy is associated with acceptable toxicity and high rates of LC, even with target undercoverage to meet OAR constraints. This suggests a potential for this approach in clinical practice and study in future trials.

Treatment of Radiation-Induced Meningiomas With Non-Invasive Stereotactic Radiosurgery

Radiation-Induced Meningiomas (RIMs) are one of the most common secondary malignancies from prior brain irradiation and are known to be recurrent. While Gamma Knife (GK) radiosurgery is routinely employed for the treatment of sporadic meningiomas, data on its use for RIMs are limited. Here, we assessed whether the use of GK radiosurgery for RIMs can achieve > 80% local control at 1 year.We retrospectively reviewed our institution's GK database from 08/31/99 - 10/08/20. Meningiomas were considered radiation-induced if they met Cahan's criteria: (1) occurred after brain radiation for a previous neoplasm, (2) were within the previous radiation field, and (3) had a distinct histology or radiographic appearance from previously treated neoplasm. Patients with a genetic predisposition for tumor formation were excluded. Endpoints included overall survival (OS), progression free survival (PFS), local failure (within 2cm of GK field), and distant failure. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.A total of 29 patients with 86 RIM lesions were identified from 1999 to 2020 and followed for a median of 59 months. Of these patients, 20 had WHO grade I (n = 4) or presumed grade I (n = 20) RIMs and 5 had WHO grade II RIMs. The median latency time from previous brain irradiation to initial SRS was 26 years. The median dose prescribed to the 50% isodose line was 14 Gy (range 12-20 Gy) with a median lesion volume of 2 cm3. The actuarial 5-yr OS and 5-yr PFS were 95% and 70%, respectively. Patients who were treated for recurrent RIMs after previous surgery had a significantly lower 5-yr OS (88% vs 100%; log-rank, P < 0.0046) and 5-yr PFS (39% vs 81%; log-rank, P < 0.005) than patients who were treated in the upfront setting. On a per-lesion basis, local control at 1-, 3-, and 5-yrs was 82%, 76%, 74%, respectively. Presumed or WHO grade I RIMs had a significantly greater 5-yr local control than WHO grade II RIMs (100% vs 56%, log-rank, P < 0.001). The rate of distant failure at 1-, 3-, and 5-yrs was 3.5%, 18%, and 32%, respectively. At time of progression, 5 patients had distant failures, while 3 patients had local and distant failures. Failures were salvaged through additional GK (n = 8), surgery (n = 2), or chemotherapy (n = 1). The crude incidence of grade 1-3 toxicity from GK was 10% (n = 3). No grade 4 or 5 adverse events were recorded. Only 1 patient developed grade 3 toxicity (cranial nerve neuropathy), which resolved with steroids.This is the largest series of RIM lesions treated with GK radiosurgery. RIMs are associated with a high OS and GK radiosurgery provides satisfactory PFS and local control. Recurrent and WHO grade II lesions are associated with lower PFS and local control after radiosurgery than upfront and WHO grade I lesions. The majority of failures after GK are distant. Treatment using GK radiosurgery has minimal morbidity. It should be considered for patients or tumors that are not candidates for surgical resection.N.Razavian: None. C.A.Helis: None. A.Laxton: None. S.B. Tatter: None. J.Bourland: None. R.T. Mott: None. G.J. Lesser: None. R.Strowd: None. M.D. Chan: None. C.K. Cramer: None.

Long-Term Outcomes in Patients With Lung Metastases Treated With Ablative Radiotherapy in the Modern Era

Metastasis-directed radiotherapy (RT) may improve disease free and overall survival (OS) in select patients with lung metastases (LM). Long-term toxicity and cancer outcome data in patients with LM treated with ablative RT is limited, particularly in patients treated concurrently with novel systemic therapies. This is a retrospective, multi-hospital analysis of ablative RT for LM.From 2015-2020, 343 LM-directed ablative RT treatment courses were delivered in 301 patients. Second primary lung cancers and non-parenchymal lesions were excluded. Medical records were reviewed retrospectively, and local progression (LP) was determined by evaluation of serial CT and/or PET scans. Univariate associations of clinical and radiographic parameters with clinical outcomes were evaluated using Cox proportional hazard models. Acute and late adverse events (AEs) were defined using CTCAE v.4.0.Median age was 64 years with 51% of patients being female. Median lesion size was 1.6 cm (range 0.3-9.4 cm). Seventy-four (22%) courses involved treatment of > 1 LM. Most common primary tumor histologies included melanoma (18%), colorectal adenocarcinoma (15%), urothelial/renal cell carcinoma (11%), and sarcoma (9%). Median physical dose was 5000 cGy. Median number of fractions delivered was 5, and 27 (8%) courses were > 5 fractions. Concurrent systemic therapies included immuno-, targeted, hormone, and cytotoxic therapy in 16%, 8%, 2%, and 1% of courses, respectively. Treatment to prior lung LM included surgery, RT, and ablation in 25%, 22%, and 2% of courses, respectively. With a median follow-up of 2.8 years, median and 5-year estimated OS were 3.0 years and 43% (95% confidence interval [CI] 34-52%), respectively. Factors associated with shorter OS included larger lesion size (P < 0.001; hazard ratio [HR] 1.2 per cm), > 2 LM (P = 0.016; HR 1.6), and > 5 fraction treatment (P = 0.024; HR 2.0). Fifteen patients experienced LP with a 5-year estimated cumulative incidence of 5.7% (95% CI 3.4-9.3%). Factors associated with increased risk of LP included larger lesion size (P = 0.004; HR 1.4 per cm), > 5 fraction treatment (P = 0.040; HR 3.8), and colorectal histology (P = 0.011; HR 3.9). Acute and late grade 2-3 AEs were 13% and 5%, respectively. There were no grade 4+ AEs. Increased toxicity was associated with larger size (P = 0.007; odds ratio 1.3 per cm) but not concurrent systemic therapy (P = 0.546) or prior treatment to other LM (P = 0.694).These data confirm the efficacy and safety of ablative RT for LM in well-selected patients. 5-year OS and LP were 43% and 6%, respectively. AEs were infrequent, even in the setting of 24% of courses delivered concurrently with systemic therapy and 40% of courses delivered subsequent to other local therapies for LM. Given the excellent OS, these data are suggestive of improved local control as a factor for improved OS.

Detection of Failure Patterns Using Advanced Imaging in Patients With Biochemical Recurrence Following Low Dose Rate Brachytherapy for Prostate Cancer

Low dose rate (LDR) brachytherapy alone or with external beam radiation (EBRT) results in excellent rates of biochemical control in patients (pts) with prostate cancer (PCa). Understanding failure patterns in pts with biochemical recurrence (BCR) may inform implant technique or pt selection. The primary objective of this study was to describe locations of recurrence on multiparametric MRI (mpMRI) and prostate specific membrane antigen (PSMA) imaging in pts with BCR after LDR brachytherapy.Pts with BCR after definitive LDR (± EBRT, ± androgen deprivation therapy (ADT)) referred for IRB approved imaging protocols were included. All pts underwent 3T mpMRI (T2 weighted, dynamic contrast-enhanced, and diffusion-weighted imaging) prospectively reviewed by prostate-dedicated radiologists. A subset of pts underwent PSMA-PET/CT imaging. Pathologic confirmation was obtained unless contraindicated. Prostate lesions were categorized as left (L)/right (R)/midline (ML); transitional zone (TZ)/peripheral zone (PZ); apical/mid/base; and anterior/posterior/central. Locations of recurrence (prostate, seminal vesicles (SV), lymph nodes (LN) and distant metastases (DM)) were recorded and reported descriptively.Between Jan 2011 and Feb 2021, 57 pts with BCR after LDR underwent prostate mpMRI. Treatment was LDR (n = 39) or EBRT + LDR (n = 18), ± ADT (n = 12). At time of LDR, initial Gleason score was ≤6 (n = 29), 7 (n = 19), 8-9 (n = 8), unknown (n = 1) and median PSA was 6 ng/mL (3.4-49). Of dosimetry available (n = 27), 2 had D90 < 90%. Median time from LDR to mpMRI was 6.7 yrs (0.8-18.3). At time of mpMRI, median pt age was 68 yrs (51-85), median PSA was 5.64 ng/mL (0.17-37.47). Lesions (n = 67) in the prostate/SV were detected in 45/57 pts on mpMRI, with a median lesion size of 1.2 cm (0.3-3.6). SV involvement was present in 20/45 patients with mpMRI detected lesions. Locations of mpMRI prostate lesions were L (n = 19) vs R (n = 16) vs ML (n = 15); TZ (n = 22) vs PZ (n = 14); apical (n = 17) vs mid (n = 25) vs base (n = 23); and anterior (n = 13) vs posterior (n = 0) vs central (n = 8). In pts with PSMA (n = 32), 31 had uptake in the prostate (n = 16, 14 detected on mpMRI) and SV (n = 12, 10 detected on mpMRI). One pt had uptake in the prostate+SV detected only on PSMA. Extraprostatic uptake on PSMA included LN (n = 15), DM (n = 5) and penile bulb (n = 1). Of 37 pts who had prostate/SV biopsy, tumor recurrence was confirmed in 31 (prostate (n = 25) and SV (n = 12)). Three of 6 pts with negative biopsy had no lesion on mpMRI. SV recurrence (imaging ± biopsy) occurred in 18/39 pts with LDR alone and in 5/18 with LDR + EBRT.In this cohort of pts with BCR following LDR, the predominant locations of local recurrence were in the anterior/central TZ and SV. PSMA corroborated the majority of mpMRI findings and often demonstrated LN and DM. These findings may inform LDR technique and impact patient selection or pre-treatment imaging evaluation; and should be confirmed in larger subsets and correlated with post-implant dosimetry.

Impact of Time Interval Between Diagnostic and Planning MRI on Tumor Volume and Anatomic Displacement for Brain Metastases Undergoing Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) is increasingly used in brain metastasis patients. However, the impact of the timing on tumor volume change and tumor anatomical displacement between the diagnostic and treatment planning imaging is not well studied.Consecutive patients diagnosed with brain metastases and treated with SRS between July, 2017 and June, 2020 were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) with identical imaging parameters were included. The impact of histology, inter-scan interval, lesion location, volume and size were evaluated on final lesion size, volume and anatomic displacement. Correlations were assessed using Kendall's rank correlation. The Kruskal Wallis rank sum test was used for all other comparisons.We included 101 eligible patients (531 lesions) with median inter-scan interval of 8 days (range: 1-42); 50% were NSCLC and 25% breast cancer. The three most common locations of lesions were the frontal (181 lesions, 34%), temporal (96, 18%), cerebellar (91, 17%) lobes. Median MRI-1 diameter and volume were 0.50 cm (Range: 0.23-0.89 cm) and 0.06 cm3 (Range: 0.01-4.62 cm3), respectively. Median percentage change in lesion diameter and volume were +9.5% (Range: -8.4% to +61.2%) and +20% (Range: -20% to +200%), respectively. Overall, there was a statistically significant change in percent tumor volume change between MRI-1 to MRI-2 (P = 0.01). Directional displacements exceeded 1 mm in 18 (3%) lesions in right to left (RL), 28 (5%) superior to inferior (SI), and 25 (4.7%) anterior to posterior (AP) directions. Overall, 355 (67%) lesions had any displacement in at least 1 direction between MRI-1 and MRI-2 and 205 (38%) in all 3 directions. Median lesion centroid displacement was 0.48 mm (0.10-3.09 mm) and was larger than 1 mm in 66 (12%) lesions. Differences were also observed across tumor histologies (P = 0.01); melanoma brain metastases had the largest magnitude changes. Tumor displacement also differed across various histologies with largest displacement in renal cell carcinoma metastases (P < 0.001). Magnitude of displacement was also significantly associated with tumor location (P = 0.03) with the largest displacement in parietal lobe lesions. Across all lesions, there was a difference in tumor size change in patients treated on corticosteroids (P = 0.01).Volumetric and positional changes can occur during the planning process for SRS and are histology and location specific. Additional analyses are key to understanding the impact of each of these variables, corticosteroids, and systemic therapy to better understand and model tumor dynamics.T. Kutuk: None. R.P. Tolakanahalli: None. A. Williams: None. M.C. Tom: Research Grant; Blue Earth Diagnostics. J.D. Vadhan: None. H. Appel: None. M.D. Hall: Research Grant; Florida Department of Health; Proton Collaborative Group (PCG) Executive Council. D. Wieczorek: None. S.D. Davis: None. M.W. McDermott: Consultant; Stryker, Diende. V. Siomin: None. M.D. Chuong: Research Grant; ViewRay, AstraZeneca. Honoraria; ViewRay, Sirtex, Accuray. Speaker's Bureau; ViewRay, Sirtex, Accuray. Advisory Board; ViewRay, Advanced Accelerator Applications. Travel Expenses; ViewRay, AstraZeneca, Accuray; Particle Therapy Cooperative Group. Manages the operations and activities within the proton center; Miami Cancer. M.P. Mehta: None. A. Gutierrez: Honoraria; ViewRay, Elekta. R. Kotecha: None.

Evolution of Blood-Brain Barrier Permeability in Subacute Ischemic Stroke and Associations With Serum Biomarkers and Functional Outcome.

Background and Purpose: In the setting of acute ischemic stroke, increased blood-brain barrier permeability (BBBP) as a sign of injury is believed to be associated with increased risk of poor outcome. Pre-clinical studies show that selected serum biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), matrix metallopeptidases (MMP), and vascular endothelial growth factors (VEGFs) may play a role in BBBP post-stroke. In the subacute phase of stroke, increased BBBP may also be caused by regenerative mechanisms such as vascular remodeling and therefore may improve functional recovery. Our aim was to investigate the evolution of BBBP in ischemic stroke using contrast-enhanced (CE) magnetic resonance imaging (MRI) and to analyze potential associations with blood-derived biomarkers as well as functional recovery in subacute ischemic stroke patients.Methods: This is an exploratory analysis of subacute ischemic stroke patients enrolled in the BAPTISe study nested within the randomized controlled PHYS-STROKE trial (interventions: 4 weeks of aerobic fitness training vs. relaxation). Patients with at least one CE-MRI before (v1) or after (v2) the intervention were eligible for this analysis. The prevalence of increased BBBP was visually assessed on T1-weighted MR-images based on extent of contrast-agent enhancement within the ischemic lesion. The intensity of increased BBBP was assessed semi-quantitatively by normalizing the mean voxel intensity within the region of interest (ROI) to the contralateral hemisphere (“normalized CE-ROI”). Selected serum biomarkers (high-sensitive CRP, IL-6, TNF-α, MMP-9, and VEGF) at v1 (before intervention) were analyzed as continuous and dichotomized variables defined by laboratory cut-off levels. Functional outcome was assessed at 6 months after stroke using the modified Rankin Scale (mRS).Results: Ninety-three patients with a median baseline NIHSS of 9 [IQR 6–12] were included into the analysis. The median time to v1 MRI was 30 days [IQR 18–37], and the median lesion volume on v1 MRI was 4 ml [IQR 1.2–23.4]. Seventy patients (80%) had increased BBBP visible on v1 MRI. After the trial intervention, increased BBBP was still detectable in 52 patients (74%) on v2 MRI. The median time to v2 MRI was 56 days [IQR 46–67]. The presence of increased BBBP on v1 MRI was associated with larger lesion volumes and more severe strokes. Aerobic fitness training did not influence the increase of BBBP evaluated at v2. In linear mixed models, the time from stroke onset to MRI was inversely associated with normalized CE-ROI (coefficient −0.002, Standard Error 0.007, p < 0.01). Selected serum biomarkers were not associated with the presence or evolution of increased BBBP. Multivariable regression analysis did not identify the occurrence or evolution of increased BBBP as an independent predictor of favorable functional outcome post-stroke.Conclusion: In patients with moderate-to-severe subacute stroke, three out of four patients demonstrated increased BBB permeability, which decreased over time. The presence of increased BBBP was associated with larger lesion volumes and more severe strokes. We could not detect an association between selected serum biomarkers of inflammation and an increased BBBP in this cohort. No clear association with favorable functional outcome was observed.Trial registration: NCT01954797.

Stereotactic body radiation therapy for adrenal gland metastases: outcome and predictive factors from a multicenter analysis.

Adrenal metastases occur in 15-35% of oncological patients. Surgery is the first treatment option. Stereotactic body radiotherapy (SBRT) has been largely explored in oligometastatic patients unfit for surgery, representing an effective and non-invasive local treatment. The results of a multi-institutional experience of SBRT on adrenal metastases in the oligorecurrent or oligoprogressive setting are herein reported. We collected data of adrenal gland metastases treated with SBRT in three Italian centers from 2010 to 2020. End-points of the present study were: Overall survival (OS), Local control of treated metastases (LC), Progression free survival (PFS), and toxicity. 149 adrenal gland metastases were treated with SBRT in 142 patients. The most common primary tumor was lung cancer (58.4%), followed by kidney cancer (9.4%). Median lesion's volume was 28.5 cm3 (2.5-323.4). The median SBRT dose was 40Gy (10-60). Median follow-up was 14.4months. One- and two-year OS were 72.3% and 53.5%. At univariate analysis performance status correlated with survival (HR 1.57, p = 0.006). One- and two-year LC were 85.4% and 79.2%, with lung primary tumor (HR 0.33, p = 0.021) and BED10 (HR 0.97, p = 0.036) significant independent factors. One- and two-year PFS were 37.7% and 24.8%. Median time to polymetastatic disease was 11.3months. Grade 1 and 2 toxicity occurred in 21 (14.7%) and 3 (2.1%) patients. The results from this large multi-center study confirm the efficacy and safety of SBRT in the management of adrenal gland metastases, as a valid alternative to other more invasive local approaches.