No Geographical Inequalities in Survival for Sarcoma Patients in France: A Reference Networks' Outcome?

The national reference network NETSARC+ provides remote access to specialized diagnosis and the Multidisciplinary Tumour Board (MTB) to improve the management and survival of sarcoma patients in France. The IGéAS research program aims to assess the potential of this innovative organization to address geographical inequalities in cancer management. Using the IGéAS cohort built from the nationwide NETSARC+ database, the individual, clinical, and geographical determinants of the 3-year overall survival of sarcoma patients in France were analyzed. The survival analysis was focused on patients diagnosed in 2013 (n = 2281) to ensure sufficient hindsight to collect patient follow-up. Our study included patients with bone (16.8%), soft-tissue (69%), and visceral (14.2%) sarcomas, with a median age of 61.8 years. The overall survival was not associated with geographical variables after adjustment for individual and clinical factors. The lower survival in precarious population districts [HR 1.23, 95% CI 1.02 to 1.48] in comparison to wealthy metropolitan areas (HR = 1) found in univariable analysis was due to the worst clinical presentation at diagnosis of patients. The place of residence had no impact on sarcoma patients' survival, in the context of the national organization driven by the reference network. Following previous findings, this suggests the ability of this organization to go through geographical barriers usually impeding the optimal management of cancer patients.

Fabrication of Radio-Opaque and Macroporous Injectable Calcium Phosphate Cement.

The aim of this work was the development of injectable radio-opaque and macroporous calcium phosphate cement (CPC) to be used as a bone substitute for the treatment of pathologic vertebral fractures. A CPC was first rendered radio-opaque by the incorporation of zirconium dioxide (ZrO2). In order to create macroporosity, poly lactic-co-glycolic acid (PLGA) microspheres around 100 µm were homogeneously incorporated into the CPC as observed by scanning electron microscopy. Physicochemical analyses by X-ray diffraction and Fourier transform infrared spectroscopy confirmed the brushite phase of the cement. The mechanical properties of the CPC/PLGA cement containing 30% PLGA (wt/wt) were characterized by a compressive strength of 2 MPa and a Young's modulus of 1 GPa. The CPC/PLGA exhibited initial and final setting times of 7 and 12 min, respectively. Although the incorporation of PLGA microspheres increased the force necessary to inject the cement and decreased the percentage of injected mass as a function of time, the CPC/PLGA appeared fully injectable at 4 min. Moreover, in comparison with CPC, CPC/PLGA showed a full degradation in 6 weeks (with 100% mass loss), and this was associated with an acidification of the medium containing the CPC/PLGA sample (pH of 3.5 after 6 weeks). A cell viability test validated CPC/PLGA biocompatibility, and in vivo analyses using a bone defect assay in the caudal vertebrae of Wistar rats showed the good opacity of the CPC through the tail and a significant increased degradation of the CPC/PLGA cement a month after implantation. In conclusion, this injectable CPC scaffold appears to be an interesting material for bone substitution.

Determinants of the access to remote specialised services provided by national sarcoma reference centres.

BACKGROUND: Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients. METHODS: Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery. RESULTS: Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities. CONCLUSIONS: In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks' organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis.

Giant Splenic Artery Pseudoaneurysms: Two Case Reports and Cumulative Review of the Literature.

BACKGROUND: Giant splenic artery pseudoaneurysms (GSAPs) > 5 cm are a rare clinical entity. The aim of this study was to present our experience with 2 such patients successfully treated by coil embolization and surgery and review the pertinent literature. METHODS: A 58-year-old woman and 57-year-old man with a history of chronic pancreatitis were diagnosed with GSAP based on computed tomography (CT) angiography. The first patient had a 6-cm pseudoaneurysm, which was successfully treated with transcatheter coil embolization using a sandwich exclusion method. The second patient had two 7-cm lesions, which were successfully treated with distal pancreatectomy and splenectomy. RESULTS: Postembolization CT angiography at 12 months showed remaining calcified pseudocyst without evidence of pseudoaneurysm in the first patient. Both patients remained well and symptom-free at 12 months. CONCLUSIONS: Combined with the experience of the previous literature, we believe that management of GSAP should be tailored for each individual case depending on the location and number of pseudoaneurysms, the underlying etiology, and the patient's hemodynamic status. Embolization should be considered as the first-line treatment for clinically stable patients with GSAP, whereas GSAPs with a pseudocyst are best treated with surgery.

A systematic review on clinical features and management of true giant splenic artery aneurysms.

BACKGROUND: True giant splenic artery aneurysms (GSAAs) >5 cm are rare and present unique therapeutic challenges. The aim of this study was to evaluate the anatomic and clinical characteristics of these lesions and the current surgical and endovascular techniques available for their treatment. METHODS: A systematic review of the literature from 2004 to 2018 and the personal experience of the authors with management of GSAAs are presented. A total of 92 GSAA cases were reviewed. Analyses were performed on anatomic and clinical features and management modalities and outcomes of GSAA, including reintervention, morbidity, and mortality. RESULTS: GSAA presented at a mean age of 56.1 ± 17.3 years, with no sex predilection; 73% were symptomatic at presentation. Abdominal pain was the presenting symptom in >50% of cases; 34% percent were ruptured, with an overall mortality rate of 12.5%. This group often presented with gastrointestinal bleeding or hemodynamic collapse. The aneurysms were almost evenly distributed across the splenic artery and were not uncommonly associated with arteriovenous fistula formation (8.7%). There were 88 patients who had surgical (53.4%), endovascular (44.3%), or combination (2.3%) therapy. The most commonly performed procedure was aneurysmectomy and splenectomy with or without additional resection. Overall, surgical treatment had a lower morbidity (P = .041) than endovascular therapy and comparable reintervention and mortality rates. CONCLUSIONS: GSAAs are uncommon vascular lesions, with distinct clinical features and aneurysm characteristics. Considering their high risk of rupture, timely diagnosis and management are essential to attain a satisfactory outcome. Surgery remains the standard treatment of these lesions. Endovascular intervention is a viable alternative in high-risk patients, particularly those with lesions <10 cm or with anomalous origin.

MRI of Tumors and Tumor Mimics in the Female Pelvis: Anatomic Pelvic Space-based Approach.

Pelvic masses can present a diagnostic challenge owing to the difficulty in assessing their origin and the overlap in imaging features. The majority of pelvic tumors arise from gastrointestinal or genitourinary organs, with less common sites of origin including the connective tissues, nerves, and lymphovascular structures. Lesion evaluation usually starts with clinical assessment followed by imaging, or the lesion may be an incidental finding at imaging performed for other clinical indications. Since accurate diagnosis is essential for optimal management, imaging is useful for suggesting the correct diagnosis or narrowing the differential possibilities and distinguishing tumors from their mimics. Some masses may require histologic confirmation of the diagnosis with biopsy and/or up-front surgical resection. In this case, imaging is essential for presurgical planning to assess mass size and location, evaluate the relationship to adjacent pelvic structures, and narrow differential possibilities. Pelvic US is often the first imaging modality performed in women with pelvic symptoms. While US is often useful to detect a pelvic mass, it has significant limitations in assessing masses located deep in the pelvis or near gas-filled organs. CT also has limited value in the pelvis owing to its inferior soft-tissue contrast. MRI is frequently the optimal imaging modality, as it offers both multiplanar capability and excellent soft-tissue contrast. This article highlights the normal anatomy of the pelvic spaces in the female pelvis and focuses on MRI features of common tumors and tumor mimics that arise in these spaces. It provides an interpretative algorithm for approaching an unknown pelvic lesion at MRI. It also discusses surgical management, emphasizing the value of MRI as a road map to surgery and highlighting anatomic locations where surgical resection may present a challenge. ©RSNA, 2019.

Pravastatin Reverses Established Radiation-Induced Cutaneous and Subcutaneous Fibrosis in Patients With Head and Neck Cancer: Results of the Biology-Driven Phase 2 Clinical Trial Pravacur.

PURPOSE: The "PRAVACUR" phase 2 trial (NCT01268202) assessed the efficacy of pravastatin as an antifibrotic agent in patients with established cutaneous and subcutaneous radiation-induced fibrosis (RIF) after head and neck squamous cell carcinoma (HNSCC) radiation therapy and/or radiochemotherapy. METHODS AND MATERIALS: The main inclusion criteria were: NSCC in remission, grade ≥2 cutaneous and subcutaneous neck RIF (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0), and no current treatment with statins or fibrates. Patients received pravastatin 40 mg/d for 12 months. The primary endpoint was reduction of RIF thickness by more than 30% at 12 months, as measured by cutaneous high-frequency ultrasonography. Secondary endpoints included RIF severity reduction, pravastatin tolerance, and quality of life. RESULTS: Sixty patients with grade 2 (n = 37), grade 3 (n = 22), or grade 4 (n = 1) RIF were enrolled from February 2011 to April 2016. The mean interval between RIF diagnosis and pravastatin initiation was 17.1 months. Pravastatin was stopped before 11 months of treatment in 18 patients (because of grade ≥2 adverse events related to pravastatin in 8 patients [13%]). In the 40 patients in whom pravastatin efficacy was assessed by high-frequency ultrasonography at baseline and at 12 months of treatment, a reduction of RIF thickness ≥30% was observed in 15 of 42 patients (35.7%; 95% confidence interval, 21.6%-52.0%). At the 12-month clinical evaluation, RIF severity was decreased in 50% of patients (n = 21; 95% confidence interval, 34.2%-65.8%), and the patients' self-perception, mood state, and social functioning were significantly improved. Pravastatin was well tolerated, with a very low occurrence of grade 3 toxicities (myalgia, n = 1) and grade 2 toxicities (myalgia/arthralgia or esophagitis, n = 3). CONCLUSIONS: This phase 2 prospective study supports the notion of radioinduced fibrosis reversibility. It showed that pravastatin (40 mg/d for 12 months) is an efficient antifibrotic agent in patients with grade ≥2 cutaneous and subcutaneous fibrosis after HNSCC radiation therapy.

Artificial nutrition in patients with cancer has no impact on tumour glucose metabolism: Results of the PETANC Study.

BACKGROUND & AIMS: Nutrition support is recommended in cachexic patients with cancer. However, there is no clear evidence about its impact on tumour growth. Glycolysis, which is usually higher in cancer than normal cells, can be monitored by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging that is widely used for cancer staging and therapy efficacy assessment. Here, we used 18F-FDG PET/CT imaging to investigate whether artificial nutrition has an impact on tumour glucose metabolism in patients with cancer and cachexia. METHODS: This prospective study included ten patients with histologically proven head and neck or oesophageal cancer. All patients underwent 18F-FDG PET/CT imaging at baseline and after (parenteral and/or enteral) nutrition support on average for 7 days. Tumour glucose metabolism changes were evaluated using static (SUVmax, SUVmean and SULpeak) and dynamic (glucose metabolic rate and transport constant rates, k) parameters computed from the 18F-FDG PET/CT data. RESULTS: Artificial nutrition (median energy intake of 21.83 kcal/kg/day [13.16-45.90], protein intake of 0.84 g/kg/day [0.56-1.64]) was administered. Eight patients (80%) received enteral nutrition and two patients (20%) parenteral support. Comparison of 18F-FDG PET/CT parameters did not highlight any significant difference in tumour glucose metabolism before and after the period of nutrition support. CONCLUSIONS: In cachexic patients with head and neck or oesophageal cancer, nutrition support administered according to the current guidelines shows no impact on tumour glucose metabolism, assessed by 18F-FDG PET/CT.

SBRT planning for liver metastases: A focus on immobilization, motion management and planning imaging techniques.

AIM: To evaluate the different techniques used for liver metastases Stereotactic Body Radiation Therapy (SBRT) planning. We especially focused on immobilization devices, motion management and imaging used for contouring. BACKGROUND: Although some guidelines exist, there is no consensus regarding the minimal requirements for liver SBRT treatments. MATERIALS AND METHODS: We reviewed the main liver metastases SBRT publications and guidelines; and compared the techniques used for immobilization, motion management, margins and imaging. RESULTS: There is a wide variety of techniques used for immobilization, motion management and planning imaging. CONCLUSIONS: We provide a subjective critical analysis of minimal requirements and ideal technique for liver SBRT planning.

Evaluation of response after SBRT for liver tumors.

Stereotactic body radiotherapy (SBRT) has developed over the last few years for the treatment of primary and metastatic hepatic tumors. The tumoral and adjacent peritumoral modifications caused by this radiosurgery limit the evaluation of response by anatomic imaging and dimensional criteria alone, such as with RECIST. This suggests that it is of interest to also take into account the residual enhancement and hyper metabolism of these hepatic targets. We have reviewed the English language literature regarding the response of hepatic lesions treated by SBRT, and found that only seven articles were specifically concerned with this problem. The response of the hepatocellular carcinoma after SBRT has been studied specifically with multiphase enhanced CT-scan. Criteria set by the European Association of Study of the Liver better estimate response at each time point of follow up than RECIST does. Non-enhancement, reflecting tumor necrosis, is additionally an early indicator of response with extended response in time and a best non-enhancement percentage is observed at 12 months. The response after treatment by SBRT of cholangiocarcinoma has not yet generated a specific report. Use of RECIST criteria is also inadequate in the evaluation of response after SBRT for hepatic metastases. Response of liver metastases to SBRT is better assessed with a combination of size and enhancement pattern. The occurrence of a lobulated enhancement during follow up is efficient to predict local progression in a specific, reproducible, and sensitive way. Patients with FDG-avid hepatic metastases are also better evaluated with PET-CT and functional criteria than routine imaging and metric evaluation alone.

Prevalence and characteristics of intravertebral enhancement on contrast-enhanced CT scans in cancer patients.

STUDY DESIGN: This was a single center, retrospective observational study. OBJECTIVE: to investigate-in a cancer population-the prevalence and hallmarks of intravertebral enhancement (IVE) detected on contrast-enhanced CT. SUMMARY OF BACKGROUND DATA: Intravertebral enhancements secondary to iodinated contrast stagnation have been described. Cancer patients have an increased risk of perivertebral venous thrombosis or stenosis secondary to several risk factors (cancer or drug induced hypercoagulability, deterioration of venous flow linked to catheter insertion, prolonged immobilization). In case of a high density lesion identified on CT, the diagnostic choice between metastasis and contrast media within bone marrow vessels may be an issue, especially as oncologic follow-up CT scans are usually performed with contrast medium injection. METHODS: 2572 contrast-enhanced body CT scans performed in cancer patients over 3 months in the medical imaging department of a university hospital were retrospectively reviewed. IVE was sought when paravertebral venous collateral circulation was detected and bone metastasis ruled out and classified as linear or nodular. Their locations within vertebra, their relation to the injection side and the predominant collateral venous network side were evaluated. RESULTS: Sixty-seven (2.8%) patients had a collateral paravertebral venous system and among them 21 had IVE (37%). There were 208 IVE locations involving 75 vertebrae. 199 IVE were linear-shaped (95.7%) and 9 nodular-shaped (4.3%). 80.8% were located between C6 and T4. 88.9% were localized in the vertebral body. 73.1% were located medially or ipsilateral to the injection side. CONCLUSION: Intravertebral enhancement is found in 37% of the patients with paraspinal collateral venous circulation when a CT scan is performed for cancer. The ipsilateral or medial position of the IVE relative to the injection side and the side of the dominant perivertebral venous system, and the possibility of connecting the IVE to a paravertebral vein may be in favor of vascular opacification.

Spinal metastases in breast cancer: single center experience.

OBJECTIVE: Metastases to the spine are a common manifestation of breast cancer leading to considerable reduction in the patient's quality of life. Physicians must consider the different treatments available to decrease pain, reduce tumor burden, and ensure spinal stability to prevent neurological compromises. The first objective of this study is to analyze the epidemiology and outcomes of patients with spinal metastases from breast cancer and describe changes over time in these lesions. The second objective is to establish the current treatment of spinal metastases in this type of cancer. METHODS: A total of 140 patients with breast cancer and spinal metastasis involvement were studied retrospectively. Demographic, clinical, and radiologic parameters were assessed, and the effects of systemic and local treatments on spinal metastasis were analyzed. RESULTS: Median patient age at diagnosis of breast cancer was 50 years (19-86 years) and average follow-up was 100 months (4-384 months). Median overall survival after diagnosis of spinal metastasis was 18.6 months. Fractures were present in 24 patients (19.3%) at diagnosis and in up to 60 cases (48.6%) by the end of the study period. CONCLUSIONS: The survival rate was better in patients with spinal metastases who received specific treatment. The evolution from lytic spinal metastasis to mixed and blastic subtypes is observed with adjunctive therapy for spinal metastases (bisphosphonates, radiotherapy). Increased attention must be given for high-grade breast cancer, as spinal metastases declare faster for these stages. This study provides evidence that a multidisciplinary tumor board specifically focusing on bone metastasis is essential to effectively manage patients with breast cancer and spinal metastasis.

Intratesticular varicocele: an easy diagnosis but unclear physiopathologic characteristics.

OBJECTIVE: Intratesticular varicocele (ITV) is an uncommon sonographic finding with controversial data concerning its prevalence and physiopathologic characteristics. The goal of this study was to determine the prevalence of ITV in a urogenital imaging department and to describe its sonographic features. METHODS: All identified cases of ITV were prospectively collected in the same imaging department. RESULTS: Intratesticular dilated veins (>2 mm) with a positive response to the Valsalva maneuver were referred to as ITV. Nine cases of ITV were detected in 8 patients (mean age, 60 years; range, 30-85 years) in a series of 1832 scrotal sonographic examinations performed over 5 years (0.4%). A history of homolateral scrotal surgery was found in 5 cases. In most cases, ITV was left sided (6/9) and located in the mediastinum testis (6/9) with associated extratesticular varicocele (8/9) and testicular hypotrophy (7/9). Five of the 7 hypotrophic testes had other causes of hypotrophy. CONCLUSIONS: Although variations do exist in the sonographic appearance of ITV, its specific sonographic and Doppler appearance should enable the radiologist to obviate further study. Intratesticular varicocele is often associated with ipsilateral testicular atrophy, but whether it is a cause or a consequence of testicular atrophy remains unclear.