A randomized phase II clinical trial of stereotactic body radiation therapy (SBRT) and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors.

BACKGROUND: Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB. METHODS: In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS). RESULTS: Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event. CONCLUSION: SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04571632 (09 AUG 2020). EUDRACT: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.

Primary splenic angiosarcoma: a case series of a rare oncological entity and diagnostic challenge.

BACKGROUND AND PURPOSE: Primary angiosarcoma of the spleen (PAS), an exceptionally rare and aggressive neoplasm with high metastatic risk (70%-85%), is frequently diagnosed in an advanced or metastatic stage. It presents diagnostic challenges due to its nonspecific symptomatology and resemblance to benign vascular lesions in various imaging modalities. PATIENTS AND METHODS: This case series aims to clarify the diagnostic difficulties by comparing imaging characteristics (CT-scan, MRI, and [18F]FDG-PET/CT) as well as pathological findings of three PAS cases diagnosed in different stages of the diseases (localized, metastatic, and metastatic with organ failure). Furthermore, a brief review on diagnostic and therapeutic features is included. RESULTS AND INTERPRETATION: We suggest [18F]FDG-PET/CT as a differentiating tool between benign and malignant splenic lesions and propose a flowchart of a diagnostic algorithm for PAS. For treatment, we advocate for early splenectomy and when systemic therapy is warranted, paclitaxel emerges as a viable first-line option. While it is crucial to acknowledge that further trial data is required to evaluate the efficacy of emerging treatment regimens, designing and conducting trials for PAS is challenging given its scarcity and aggressive behavior. Therefore case reporting remains important.

Phase II Trial Assessing the Repeatability and Tumor Uptake of [68Ga]Ga-HER2 Single-Domain Antibody PET/CT in Patients with Breast Carcinoma.

Human epidermal growth factor receptor 2 (HER2) status is used for decision-making in breast carcinoma treatment. The status is obtained through immunohistochemistry or in situ hybridization. These two methods have the disadvantage of necessitating tissue sampling, which is prone to error due to tumor heterogeneity or interobserver variability. Whole-body imaging might be a solution to map HER2 expression throughout the body. Methods: Twenty patients with locally advanced or metastatic breast carcinoma (5 HER2-positive and 15 HER2-negative patients) were included in this phase II trial to assess the repeatability of uptake quantification and the extended safety of the [68Ga]Ga-NOTA-anti-HER2 single-domain antibody (sdAb). The tracer was injected, followed by a PET/CT scan at 90 min. Within 8 d, the procedure was repeated. Blood samples were taken for antidrug antibody (ADA) assessment and liquid biopsies. On available tissues, immunohistochemistry, in situ hybridization, and mass spectrometry were performed to determine the correlation of HER2 status with uptake values measured on PET. If relevant preexisting [18F]FDG PET/CT images were available (performed as standard of care), a comparison was made. Results: With a repeatability coefficient of 21.8%, this imaging technique was repeatable. No clear correlation between PET/CT uptake values and pathology could be established, as even patients with low levels of HER2 expression showed moderate to high uptake. Comparison with [18F]FDG PET/CT in 16 patients demonstrated that in 7 patients, [68Ga]Ga-NOTA-anti-HER2 shows interlesional heterogeneity within the same patient, and [18F]FDG uptake did not show the same heterogeneous uptake in all patients. In some patients, the extent of disease was clearer with the [68Ga]Ga-NOTA-anti-HER2-sdAb. Sixteen adverse events were reported but all without a clear relationship to the tracer. Three patients with preexisting ADAs did not show adverse reactions. No new ADAs developed. Conclusion: [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT imaging shows similar repeatability to [18F]FDG. It is safe for clinical use. There is tracer uptake in cancer lesions, even in patients previously determined to be HER2-low or -negative. The tracer shows potential in the assessment of interlesional heterogeneity of HER2 expression. In a subset of patients, [68Ga]Ga-NOTA-anti-HER2-sdAb uptake was seen in lesions with no or low [18F]FDG uptake. These findings support further clinical development of [68Ga]Ga-NOTA-anti-HER2-sdAb as a PET/CT tracer in breast cancer patients.

MR of tendons about the hip: A study in asymptomatic volunteers.

PURPOSE: Tendon pathology around the hip is a common entity. The aim of this study was to detect tendon abnormalities around the hip in a population of asymptomatic volunteers. MATERIALS AND METHODS: Fifty volunteers (100 hips) referred for non-musculoskeletal conditions were evaluated with an additional coronal STIR-weighted MRI imaging on a 1.5 MR unit. This group was composed of 27 women and 23 men with a mean age of 52 (19-91 years). The images were interpreted independently by 2 musculoskeletal radiologists. All tendons around the hip were given a score from 0 to 4, with a score 0 corresponding to no abnormality, score 1 to signal alteration around the tendon, score 2 to minimal signal abnormality in the tendon, score 3 partial tear and score 4 complete rupture. The trochanteric bursa was also evaluated and its size was measured. It was also given a score from 0 to 3 (0: no abnormality, 1: slight hypersignal, 2: bursitis < 10 mm, 3: bursitis ≥ 10 mm). RESULTS: High intratendinous signal was commonly found at the joined insertion of biceps femoris and semitendinosus (18% L, 20% R), the semimembranosus (24% L, 20% R), gluteus minimus (6% L, 11% R) and rectus femoris (9% L, 3% R). A small trochanteric bursa was seen in 33% of the volunteers on the left side and 32% on the right side. The interobserver correlation was very good with an intraclass correlation coefficient of 0.79 (CI: 0.74-0.85). CONCLUSION: Slight signal alterations might be found in the insertions of the rectus femoris, hamstrings and gluteus minimus tendons. A small to moderate trochanteric bursitis might also be seen. This suggests that care should be taken when interpreting MR scans to attribute symptoms to these findings.

A Curious Case of Recurrent Abdominal Wall Infections.

An 82-year-old male was transferred for an abdominal CT scan for chronic cutaneous fistulation at the level of the right abdominal wall. Previous CT and ultrasound imaging described recurrent collections in the right abdominal wall, requiring CT guided abscess drainage. The abdominal CT scan revealed an abscess in between the internal oblique and transversus abdominis muscle layers of the right flank, with significant fat stranding and loss of the intermuscular fat planes ( Figure 1 ). Inside this abscess, we notice a spontaneous hyperdense nodular lesion (Hounsfield Units 130), which doesn't enhance after contrast injection ( Figure 1 arrow). Looking back at the previous CT scans we discern the presence of this hyperdense lesion, which tends to migrate over time over a small distance along the abdominal wall ( Figure 2 A-D arrow). We can trace this back on the numerous previous scans, with different local tissue reactions over time. The first performed CT 8 years prior reveals a perforated calculous cholecystitis, containing multiple cholecystolithiases with the same density as our previously mentioned hyperdense lesion ( Figure 3 arrow). Thus, raising the suspicion of a biliary origin of this corpus alienum. TEACHING POINT: Spilled gallstones during laparoscopy may lead to late abscess.

Systemic generalised lymphangiomatosis: unknown aetiology and a challenge to treat.

We describe a case of a woman diagnosed at the age of 35 years with a generalised mediastinal and abdominal lymphangiomatosis associated with a protein losing enteropathy, who successfully improved when treatment with sirolimus was initiated.

Fat misbehaving in the abdominal cavity: a pictorial essay.

Intra-abdominal fat is abundantly present in both the peritoneum and retroperitoneum. Fat necrosis or inflammation are common findings in abdominal imaging. The most common pathologies that we encounter are epiploic appendagitis, omental infarction, mesenteric panniculitis, and encapsulated fat necrosis. Less common entities that can occur are pancreatic saponification, heterotopic mesenteric ossification, and pseudolipoma of the capsule of Glisson. These entities can mimic more urgent pathologies such as appendicitis, diverticulitis, or malignancies.

Ulcerated gastrointestinal stromal tumor causing a gastrogastric intussusception.

When a gastrointestinal intussusception is found, an underlying lesion should be excluded.

Can tumor coverage evaluated 24 h post-radiofrequency ablation predict local tumor progression of liver metastases?

PURPOSE: To assess the predictive value for local tumor progression (LTP) of geometrical tumor coverage using the contrast-enhanced (ce-)CT images acquired before and within 24 h after radiofrequency (RF) ablation. METHODS: Twenty patients (6 male and 14 female, median age 62 years) with 45 focal hypovascular liver metastases (16 colorectal carcinoma, 3 melanoma and 1 breast carcinoma) underwent RF ablation under CT-guidance and received a ce-PET/CT scan within 24 h post-procedure. Pre- and post-ablation ce-CT-images were aligned using an interactive procedure and used to verify the tumor coverage of the RF ablation. Results were correlated to LTP as recorded during follow-up performed every 2-3 months after the intervention (mean follow-up of 110 weeks) and compared to standard reading performed by three readers of the ce-CT images. RESULTS: Eleven tumors (25%) showed LTP during the follow-up period. One lesion, which did not show LTP, was excluded from analysis due to the poor quality of the alignment. For the remaining, 29 (66%) tumors were completely covered by the ablation zone, 9 (20%) were not, and for 6 (14%) tumors the edges coincided with the edge of the ablation zone. The sensitivity, specificity, PPV and NPV for LTP of having incomplete tumor coverage or no apparent ablative margin versus standard reading of ce-CT were 100, 88, 73 and 100% versus 42, 88, 58 and 82%, respectively. CONCLUSIONS: Verifying the tumor coverage of liver metastases by an ablation zone through alignment of pre- and early post-ablation ce-CT images has a high predictive value for LTP.

Comparative Interpretation of CT and Standard Radiography of the Pleura.

Many diseases affect the pleural space in both adults and children, including common diseases such as pneumonia, cancer and heart failure. Pleural effusion is the most common manifestation of pleural disease, and it is often a secondary effect of another disease process. Imaging plays a crucial role in the management of pleural disease. Chest radiography often remains the first examination in the assessment of these patients. Depending on the clinical context, the optimal imaging technique for further evaluation might be computed tomography (CT), ultrasound (US), or magnetic resonance (MR).

Ureteral Metastasis: Uncommon Manifestation in Prostate Cancer.

Ureteral metastasis from a primary prostate cancer is a rare event in the initial diagnosis and progression of prostate cancer. We report here the case of a 72- year-old patient who was treated for castration-resistant metastatic prostate cancer involving bone, intra-abdominal lymph nodes, bilateral adrenal glands, and a small distal ureteral lesion with left hydronephrosis considered in remission, with a luteinizing hormone-releasing hormone analog plus abiraterone acetate (AA) and prednisone after initial docetaxel plus prednisone chemotherapy. After an episode of acute left flank pain, the previous left distal intraluminal ureteral mass appeared increased in volume on computed tomographic scan and was compatible with either a metastasis from prostate cancer, transitional cell carcinoma of the ureter, or a collision tumor. After left nephroureterectomy (NU), the mass was confirmed to be of prostatic origin on histopathological examination and the only site of metastatic progression of prostate cancer. Abdominal CT-scan and the operative specimen of the NU showed no direct extension of the abdominal lymph nodes into the ureteral lesion. We speculate that this unique ureteral prostate cancer metastasis was the result of hematogenic spread of prostate cancer, although microscopic spread through the lymphatic system could not be excluded. The transient anti-tumor effect of AA plus prednisone at the level of ureteral metastasis, as far as we are aware of, has never been documented before.

Dual-energy CT after radiofrequency ablation of liver, kidney, and lung lesions: a review of features.

Early detection of residual tumour and local tumour progression (LTP) after radiofrequency (RF) ablation is crucial in the decision whether or not to re-ablate. In general, standard contrast-enhanced computed tomography (CT) is used to evaluate the technique effectiveness; however, it is difficult to differentiate post-treatment changes from residual tumour. Dual-energy CT (DECT) is a relatively new technique that enables more specific tissue characterisation of iodine-enhanced structures because of the isolation of iodine in the imaging data. Necrotic post-ablation zones can be depicted as avascular regions by DECT on greyscale- and colour-coded iodine images. Synthesised monochromatic images from dual-energy CT with spectral analysis can be used to select the optimal keV to achieve the highest contrast-to-noise ratio between tissues. This facilitates outlining the interface between the ablation zone and surrounding tissue. Post-processing of DECT data can lead to an improved characterisation and delineation of benign post-ablation changes from LTP. Radiologists need to be familiar with typical post-ablation image interpretations when using DECT techniques. Here, we review the spectrum of changes after RF ablation of liver, kidney, and lung lesions using single-source DECT imaging, with the emphasis on the additional information obtained and pitfalls encountered with this relatively new technique. Teaching Points •Technical success of RF ablation means complete destruction of the tumour. •Assessment of residual tumour on contrast-enhanced CT is hindered by post-ablative changes. •DECT improves material differentiation and may improve focal lesion characterisation. •Iodine maps delineate the treated area from the surrounding parenchyma well.

Predictive value of pattern classification 24 hours after radiofrequency ablation of liver metastases on CT and positron emission tomography/CT.

PURPOSE: To assess a classification scheme for predicting local tumor progression (LTP) after radiofrequency (RF) ablation of liver metastases, using predefined patterns on contrast-enhanced computed tomography (CT) and positron emission tomography (PET) combined with CT (PET/CT) acquired 24 hours after RF ablation. MATERIALS AND METHODS: There were 45 metastases in 20 patients treated. After 24 hours, imaging of the ablation zones was performed with contrast-enhanced PET/CT. Three independent radiologists prospectively assessed contrast-enhanced CT and combined PET/CT images to identify three patterns: pattern I, no tissue enhancement or fluorodeoxyglucose uptake between the ablation zone and the liver parenchyma; pattern II, a rimlike pattern; and pattern III, a peripheral nodule. PET/CT images obtained after 8-10 weeks were evaluated for LTP. The patterns were analyzed for their sensitivity, specificity, positive predictive value, and negative predictive value for predicting LTP. RESULTS: Pattern I was most frequently observed (81% for contrast-enhanced CT and 61% for PET/CT) as well as for ablation zones that showed LTP (52% and 37%, respectively). Conversely, pattern II was observed for tumors that were completely ablated (6% and 29%, respectively). Patterns II and III together had the highest sensitivity for predicting LTP (48% and 63%, respectively); pattern III had the highest specificity (94% and 95%, respectively). For nodular patterns, test characteristics were better for PET/CT compared with contrast-enhanced CT, but the difference was not significant. Nodular patterns > 1 cm achieved high positive predictive value (both 100%). CONCLUSIONS: Inflammation and hyperemia can hinder interpretation on imaging 24 hours after RF ablation, especially on PET/CT. Nodular patterns around the ablation zone on early contrast-enhanced CT and PET/CT have a high predictive value for LTP and should be taken into account for disease management.

Single-center experience with ipilimumab in an expanded access program for patients with pretreated advanced melanoma.

Ipilimumab, a CTLA-4-blocking monoclonal antibody, improved the overall survival (OS) of advanced melanoma patients treated in prospective clinical trials. We here report a study on the outcome of patients with pretreated advanced melanoma offered ipilimumab (at its licensed dose of 3 mg/kg, every 3 wk for a total of 4 doses) in an expanded access program at a single-center university hospital. Of the 50 patients initiating ipilimumab, 31 patients completed induction therapy and 9 patients were offered reinduction therapy. Most immune-related adverse events were mild and reversible. The best objective response rate by mWHO-criteria included 1 complete response and 4 partial responses (best objective response rate of 10%). Two additional patients obtained a partial response by immune-related response criteria. Median OS was 7 months, with a 1- and 2-year survival rate of 45.2% and 28.8%, respectively. Long-term disease control with ipilimumab was observed in 7 patients of which 4 received reinduction. Baseline serum C-reactive protein (CRP) and the absolute lymphocyte count (ALC) measured on week 6 significantly correlated with OS. In conclusion, in this single-center experience with ipilimumab for advanced pretreated melanoma patients, clinical outcome was comparable with the results of published prospective studies. Reinduction therapy was of importance for maintaining long-term disease control in the majority of responding patients. Baseline CRP and ALC at week 6 deserve further prospective evaluation as prognostic and/or predictive (surrogate) markers.

Initial assessment of tumor tracking with a gimbaled linac system in clinical circumstances: a patient simulation study.

PURPOSE: To have an initial assessment of the Vero Dynamic Tracking workflow in clinical circumstances and quantify the performance of the tracking system, a simulation study was set up on 5 lung and liver patients. METHODS AND MATERIALS: The preparatory steps of a tumor tracking treatment, based on fiducial markers implanted in the tumor, were executed allowing pursuit of the tumor with the gimbaled linac and monitoring X-rays acquisition, however, without activating the 6 MV beam. Data were acquired on workflow time-efficiency, tracking accuracy and imaging exposure. RESULTS: The average time between the patient entering the treatment room and the first treatment field was about 9 min. The time for building the correlation model was 3.2 min. Tracking errors of 0.55 and 0.95 mm (1σ) were observed in PAN/TILT direction and a 2D range of 3.08 mm. A skin dose was determined of 0.08 mGy/image, with a source-to-skin distance of 900 mm and kV exposure of 1 mAs. On average 1.8 mGy/min kV skin dose was observed for 1 Hz monitoring. CONCLUSION: The Vero tracking solution proved to be fully functional and showed performance comparable with other real-time tracking systems.

Unusual Appearance of a Pendulated Gastric Tumor: Always Think of GIST.

Objective. To investigate the clinicopathological characteristics of gastrointestinal stromal tumor (GIST) with significant cystic changes and to assess the molecular genetic characteristics. Methods. In a 68-year-old man, a large abdominal tumoral mass was discovered incidentally. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of a large cystic lesion with multiple contrast-enhancing septae and papillary projections. No clear connection with any of the surrounding organs was identified. Malignancy could not be excluded, and surgery was indicated. During surgery, the large mass was found to be attached by a narrow stalk to the large curvature of the stomach. Results. The histological features and immunohistiochemical profile of the tumor cells (positivity for CD117 and CD34) were consistent with a gastrointestinal stromal tumor with a high risk of progressive disease according to the Fletcher classification. Diagnosis was confirmed by mutational analysis; this demonstrated mutation in exon 14 of PDGFRA. During the followup of 97 months, the patient had a cancer-free survival. Conclusions. This case demonstrates that gastrointestinal stromal tumors (GISTs) with extensive cystic degeneration should be considered in the differential diagnosis of a cystic abdominal mass.

Sarcoidosis in a patient with metastatic melanoma sequentially treated with anti-CTLA-4 monoclonal antibody and selective BRAF inhibitor.

A female patient with stage IV-M1c (distant lymph node and breast metastases), chemotherapy-refractory melanoma was treated with the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-inhibitory monoclonal antibody ipilimumab. At first evaluation following induction treatment, there was marked increase in the volume of the lymphadenopathies (including new adenopathies) and strong uptake of (18)Fluorodeoxy-D-glucose ((18)FDG); marked enlargement of the spleen and interstitial lung infiltrates were also observed. Non-necrotising granulomas were discovered on transbronchial mucosal biopsy and cytology on bronchoalveolar lavage established the diagnosis of sarcoidosis. There was a marked clinical and (18)FDG-positron emission tomography/computed tomography ((18)FDG-PET/CT) documented response following six weeks of corticotherapy. At follow-up, progression of subdiaphragmatic melanoma lymph node metastases was documented. Regression of these metastatic sites was observed during treatment with the selective v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib. The patient died due to progressive disease after three months of vemurafenib treatment. Our case report illustrates the need to take into consideration exacerbation of sarcoidosis as a potential confounder in the assessment of tumor response in a melanoma patient treated with the anti-CTLA-4 mononclonal antibody ipilimumab.

Restoration of tumor equilibrium after immunotherapy for advanced melanoma: three illustrative cases.

Metastatic melanoma runs a predictable detrimental course in the vast majority of patients. New modalities of immunotherapy, such as melanoma antigen-specific therapeutic vaccination and cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor blockade by monoclonal antibodies (mAbs), have been associated with atypical kinetics of tumor response that differ from those observed during cytotoxic treatment. Recently, new tumor response criteria have been proposed based on the tumor response characteristics observed in clinical studies with ipilimumab (the so-called 'immune-related response criteria'). We report three illustrative cases of the American Joint Committee on Cancer stage IV-M1c melanoma patients who experienced atypical kinetics of tumor response to the treatment with the CTLA-4-blocking mAb, ipilimumab (case 1), or an autologous dendritic cell vaccine in combination with interferon α-2b (cases 2 and 3). These cases show that atypical response patterns not only relate to the outcome of CTLA-4-blocking mAb therapy but also to the treatment with therapeutic vaccines and interferon α-2b.

Image-guided marker placement in liver tumors for stereotactic radiotherapy: technique and safety.

PURPOSE: To evaluate the technique and safety of percutaneous radiopaque gold marker placement in the liver before external stereotactic radiotherapy for intrahepatic tumors. MATERIALS AND METHODS: Thirteen patients were included in this study. One gold marker per patient was placed using a computed tomographic fluoroscopy procedure. Follow-up was carried out with a multislice computed tomographic scan. RESULTS: A marker was placed in the center (n = 6) or in the periphery (n = 7) of the target lesion. No immediate complications were noted. Long-term follow-up showed changes in coil position relative to liver anatomy in 4 cases; all 4 markers were placed in the center of the target lesion. No other long-term complications were seen. CONCLUSIONS: Radiopaque markers can be placed safely in liver lesions before external stereotactic radiotherapy. However, marker displacement can occur early, thereby compromising the precision of the planned treatment. The decreased size of the tumor as a response to therapy was responsible for late migration in this small series.

Combined hepatocellular and cholangiocellular carcinoma presenting with radiological characteristics of focal nodular hyperplasia.

Combined hepatocellular and cholangiocellular carcinoma (cHCC-CC) is a rare tumor type containing unequivocal elements of both hepatocellular carcinoma and cholangiocarcinoma that are intimately mixed. Although these tumors are usually considered to be more related to hepatocellular carcinoma than to cholangiocarcinoma, they sometimes, in contrast to hepatocellular carcinoma, contain a significant amount of fibrous stroma. This might in some cases explain atypical radiological features. We report a case of a cHCC-CC in a 47-year-old female that resembled focal nodular hyperplasia on Magnetic Resonance Imaging. Correlation of imaging and serum levels of alpha-fetoprotein and CA19.9 can help to make the correct diagnosis preoperatively.