Can 18F-FDG PET/CT findings be used to predict orbital tumor histology?

PURPOSE: To investigate whether 18F-FDG PET/CT might be useful to predict the histology of various orbital tumors based on the maximum standard uptake value (SUVmax) and the OMSUV (orbital max SUV)/MLSUV (mean liver SUV) ratio. PATIENTS AND METHODS: A retrospective single-center study was conducted between May 2019 and December 2020. Patients with an orbital mass who underwent preoperative 18F-FDG PET/CT followed by an orbital biopsy were included. Tumor histology was classified as follows: orbital inflammation, solid tumor, low-grade lymphoid tumor, and high-grade lymphoid tumor. Orbital tumors were also classified as indolent or aggressive. Data recorded included the orbital SUVmax, OMSUV/MLSUV ratio and additional extra-orbital SUV sites. RESULTS: Forty-five patients (24 men) were included. There were 15 (33.3%), 14 (31.1%), 9 (20%), and 7 (15.5%) cases of orbital inflammation, solid tumor, low-grade lymphoid tumor, and high-grade lymphoid tumor, respectively. No correlation was found between the OMSUV/MLSUV ratio and orbital SUVmax and tumor histology (Z = -0.77, Z = -0.6, Z = -1.6, and Z = 0.94, all P > 0.05, respectively). No correlation was found between the OMSUV/MLSUV ratio (Z = -1.42, P > 0.05) and orbital SUVmax (Z = -0.82, P > 0.05) and tumor aggressiveness (indolent versus aggressive). Subgroup analyses showed that SUVmax was predictive of lymphoma aggressiveness (P = 0.05) and was able to distinguish orbital cancers (all lymphomas+solid tumors) from benign tumors (P = 0.02). CONCLUSION: 18F-FDG PET/CT could not be used to predict the underlying orbital tumor histology. However, more aggressive tumors, especially high-grade lymphomas and cancers, tended to have a higher orbital SUVmax compared to indolent lesions.

Epidemiology of candidemia in NICE area, France: A five-year study of antifungal susceptibility and mortality.

OBJECTIVES: The aim of this study was to investigate the epidemiology of candidemia, the fungal susceptibility, the first-line therapy and the morality rate over 5 years. Knowing the differences of the yeasts in the candidemia local epidemiology, is essential to obtain information on fungal epidemiology to adapt antifungal strategies. MATERIALS/METHODS: This retrospective study was conducted from January 2014 to December 2018. The susceptibility of the Candida strains were tested for amphotericin B, caspofungin, voriconazole and fluconazole. RESULTS: The 304 strains were isolated from 290 patients (40 patients in 2014, 65 in 2015, 72 in 2016, 62 in 2017 and 51 in 2018). The three most common Candida spp isolated from blood cultures were Candida albicans (44%), Candida glabrata (22%) and Candida parapsilosis (13%). The proportion of non-albicans Candida decreased from 68% in 2014 to 45% in 2018. C. albicans and C. parapsilosis were to the four antifungals tested. As first-line therapy, 60% of patients received caspofungin and 26% fluconazole. There was no significant difference in the mortality between the two arms of patients (, 27% and 21%, p = 0.47 at 30 days respectively). Thirty day all-cause mortality was 31% and it decreased from 2014 (46%) to 2018 (18%). CONCLUSIONS: We report that the absence of antifungal resistance of our C. albicans and C. parapsilosis candidemia suggests possible treatment after MALDI-TOF identification with fluconazole as first-line therapy in our hospital, as soon as possible and while continuing to perform the antifungal test.

Efficacy and safety of an artificial dermal graft for the reconstruction of exenterated sockets: a preliminary report.

PURPOSE: The purpose of this study is to report our experience with the use of artificial dermis grafts for orbital socket reconstruction following orbital exenteration (OE). METHOD: A retrospective study was conducted in our ocular oncology centre from May 2018 to June 2020 in patients undergoing OE for orbital malignancies in whom an artificial dermis device (Integra® template, 2 layers) was used for reconstruction. Data recorded included demographics, previous and adjuvant treatments, aetiologies, surgical procedure, surgical reconstruction, complications and follow-up. The main outcome measure was the time between OE and the full granulation of the cavity. RESULTS: Ten patients (mean age, 71.3 years [43-92]) were included. Tumours originated from the conjunctiva (n = 5, 50%), eyelid (n = 3, 30%) and orbit (n = 2, 20%). Nine patients underwent total OE, and one required enlarged OE. Orbital reconstruction was performed using an artificial dermis alone (n = 9, 90%) or combined with regional flaps (n = 1, 10%). The mean granulation time was 3.3 weeks (2-4). Three (30%) patients received adjuvant radiotherapy 1 month post-surgery. The mean time to spontaneous epithelialization was 9.4 weeks (6-12). Preoperative and postoperative radiotherapy was not associated with a delayed epithelialization of the socket (p = 0.463 and p = 0.236, respectively). One (10%) and 2 (20%) patients experienced postoperative socket infection and an ethmoidal fistula, respectively. The mean follow-up was 11.6 months (6-16). CONCLUSION: Using artificial dermis grafts alone or with regional flaps appears to be a viable surgical procedure for orbital socket reconstruction. They reduce surgical morbidity and hospital stay. Preoperative and postoperative radiotherapy does not seem to delay socket healing.

Incidence of Orbital Exenteration: A Nationwide Study in France over the 2006-2017 Period.

PURPOSE: Orbital exenteration is a radical and disfiguring surgery mainly performed for treating orbital malignancies. Recently, several studies found favorable results in terms of overall survival with eye-sparing surgeries combined with targeted therapies and/or radiotherapy. The aim of this study was to assess the incidence of orbital exenteration and its evolution in France between 2006 and 2017. METHODS: A national observational cohort study was conducted in France between January 2006 and December 2017. Data were collected from the national PMSI (Programme de Médicalisation des Systèmes d'Information) database provided by the CNAM (Caisse Nationale de l'Assurance Maladie). All patients undergoing orbital exenteration over the study period in France were included. RESULTS: One thousand and fifty-seven patients were included. The mean annual number of orbital exenterations was 88.1 (63-117), corresponding to a mean incidence of 0.1/100,000 inhabitants/year. A male predominance was noted (n = 626, 59.2%). Exenteration was mainly performed between 75 and 79 years. The underlying etiology was available for 821 patients (77.7%): malignancies were the most common (n = 755; 92.0%) followed by infectious diseases (n = 16; 1.9%). Over the study period, no statistical difference in the mean incidence of orbital exenteration was found (p = .132). CONCLUSION: The mean annual incidence of orbital exenteration was 0.1/100,000 inhabitants in France and was not significantly modified during the study period.

[Does orbital exenteration still has a place in 2019?] / L'exentération orbitaire a-t-elle encore sa place en 2019 ?

INTRODUCTION: Orbital exenteration is a radical anatomically and psychologically disfiguring procedure. It is mostly performed for management of orbital cancers or cancers with orbital involvement. The lack of benefit in terms of overall survival and the development of new molecular therapies (targeted therapies, immunotherapy) in recent years leads us to question its use. The goal of our review is to answer to the following question: is orbital exenteration a viable procedure in 2019? MATERIALS AND METHODS: A literature review was performed using the PUBMED and MEDLINE databases. The following terms were used then crossed with each other: "orbital exenteration", "exenterated socket", "overall survival", "life expectancy", "orbital reconstruction", "socket reconstruction". Oncology articles from the past 15 years were included and separated into those in the oculoplastic literature and those in the ENT literature. RESULTS: Nineteen articles were included in this review. Eyelid tumours represent the main etiology of orbital exenteration. Basal cell carcinoma is the most frequently incriminated tumor, while sebaceous carcinoma and conjunctival squamous cell carcinoma are the most frequently encountered in Asian series. Non-conservative orbital exenteration is the most prevalent surgery performed. Orbital reconstruction depends on the surgeon's speciality: healing by secondary intention and split thickness skin grafts are mostly performed by oculoplastic surgeons, whereas regional or free flaps are mostly performed by ENT surgeons. Cerebrospinal fluid leakage is the most common intraoperative complication, encountered in 0 to 13 % of cases. The most common postoperative complications are ethmoid fistula and infection of the operative site, encountered in 0 to 50 % and 0 to 43 % of cases respectively. Orbital exenteration allows surgical resection of R0 tumors in 42.5 % to 97 % of cases. Overall survival following orbital exenteration is 83 % (50.5-97) and 65 % (37-92) at 1 and 5 years respectively. Identified risk factors for poor overall survival are: age, tumor histology (worse prognosis with choroidal melanoma, better prognosis with basal cell carcinoma), non-R0 surgical resection, locally advanced tumors (size>20mm, BCVA<20/400 and the presence of metastases at diagnosis). Recent studies have demonstrated favorable outcomes when managing locally advanced basal cell carcinoma, lacrimal gland cancer and conjunctival melanoma with targeted therapies or immunotherapies without performing orbital exenteration. CONCLUSION: Orbital exenteration remains a major part of our therapeutic arsenal. Although orbital exenteration has failed to demonstrate any overall survival benefit, it allows satisfactory local control of the disease with an increasingly less invasive procedure. The development of targeted therapies and immunotherapies may change our therapeutic decisions in the future.

[Local, regional and systemic dissemination of choroidal melanoma : Clinical and pathological correlation from 2 cases]. / Dissémination locorégionale et systémique du mélanome choroïdien : corrélation anatomoclinique à partir de 2 cas.

PURPOSE: To describe didactically the local, regional and systemic spread of choroidal melanoma. PATIENTS AND METHODS: Two patients who had undergone primary enucleation for the management of choroidal melanoma in 2018 at the University Hospital of Nice were included. Extrascleral extension and invasion of the vortex veins were evaluated, as well as synchronous and metachronous metastases, based on our database. RESULTS: Patient 1 was diagnosed with large choroidal melanoma with partial scleral invasion and vortex vein involvement. Cytogenetic analysis demonstrated a loss of chromosome 3, and a gain of chromosome 8q. Systemic work-up was unremarkable. Patient 2 was diagnosed with a large choroidal melanoma with extrascleral extension and vortex vein involvement. Cytogenetic analysis demonstrated a loss of chromosome 3 and a gain of chromosome 8q. Systemic work-up revealed several liver metastases. A total of 1762 patients were included in our database. Eighty-five patients (4.8 %) and 46 patients (2.6 %) experienced vortex vein invasion and extrascleral extension respectively. Patients with vortex vein invasion were diagnosed with synchronous and metachronous liver metastases in 1.2 % and 18.8 % respectively. Patients with extrascleral extension had synchronous and metachronous liver metastases in 6.5 % and 30.4 % respectively. The mean follow-up was 49.4 months (1-180). CONCLUSION: Extrascleral extension and vortex vein invasion illustrate the local, regional and systemic spread of choroidal melanoma. The latter are often associated with genetically aggressive tumours associated with high metastatic risk.

First endogenous fungal endophthalmitis due to Fusarium dimerum: A severe eye infection contracted during induction chemotherapy for acute leukemia.

Endophthalmitis is a rare infection of the vitreous and/or aqueous. It can be bacterial or fungal. Exogenous endophthalmitis is the most common form and results from direct inoculation of a pathogen after eye surgery or penetrating trauma. Endophthalmitis can also be endogenous, secondary to disseminated infection. Fungal endophthalmitis is associated with poor prognosis and treatment is difficult given the low penetration of most of the antifungal agents available and the emergence of resistant filamentous fungi like Fusarium. To our knowledge, we describe the first endogenous fungal endophthalmitis due to Fusarium dimerum, a ubiquitous pathogen found in soil and plants. A 71-year-old woman, diagnosed with acute myeloid leukemia, was hospitalized for surveillance after induction chemotherapy. Prophylaxis by antibiotics and posaconazole was ongoing when she complained of pain and decreased vision in the left eye. A voluminous chorioretinal abscess developed and after multiple sterile aqueous humour samples, only vitrectomy allowed diagnosis with fungal hyphae seen on May-Grünwald Giemsa stained smear and positive cultures. The fungus was identified as Fusarium dimerum. The treatment, that included intravitreal injections of voriconazole and amphotericin B associated with systemic administration of voriconazole, allowed complete control of the infection. The source of this infection could not be confirmed despite the discovery of several possible infection sites including a periungual whitlow on the left hand and a lesion on a nail, from which samples were negative in microbiology laboratories. Unfortunately, damages of the retina were too important and the patient did not recover sight of her left eye.

Description of late onset neutropenia in indolent lymphoma patients treated with bendamustine plus rituximab.

Bendamustine (B) associated with rituximab (R) is widely described in literature for the management of patients with chronic lymphoid leukaemia (CLL) and indolent non-Hodgkin lymphoma. Safety data regarding late hematotoxicity such as late onset neutropenia (LON) are scarce. The aim of our study was to assess the incidence and to identify risk factors for LON in patients with indolent non-Hodgkin lymphoma and CLL treated with B and R (B-R). One hundred forty five patients were treated with B-R as first or second line. Patients with neutropenia prior induction treatment, treated beyond second line and relapsing within 3 months after the end of induction treatment, were excluded. Patients receiving at least 1 cycle of B-R and having LON during follow-up period were included and considered as eligible for toxicity assessment. A complete blood count was performed 4 weeks after the last cycle of induction treatment and thereafter every 3 months for 1 year. Thirty six patients were identified in our cohort (incidence of 25%), mostly affected by CLL (n = 11) and follicular lymphoma (FL) (n = 15). During follow-up, 84 events of LON were recorded, 61% and 39% were of grades 1/2 and 3/4, respectively. No episode of febrile neutropenia was documented. Amongst 13 of the 15 patients with FL undergoing R maintenance, 8 had treatment discontinuation because of LON. Median time for LON (grade > 2) and time to recovery (grade < 3) were of 11.2 and 17.3 weeks, respectively. One year after B-R induction, LON persisted in 4 patients. The risk of LON was increased both in patients with FL or CLL and performance status >1. The LON in B-R treated patients is clinically relevant. Close clinical and biological follow-up and treatment prophylaxis (eg, valaciclovir and cotrimoxazole) especially for FL patients undergoing maintenance with R monotherapy seems relevant.

Meningeal SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B member 1 (SMARCB1)-deficient tumours: an emerging group of meningeal tumours.

AIMS: Bi-allelic inactivation of SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B member 1 (SMARCB1; also known as INI1) and loss of immunohistochemical expression of SMARCB1 define the group of SMARCB1-deficient tumours. Initially highlighted in malignant rhabdoid tumours, this inactivation has subsequently been observed in several intra and extracranial tumours. To date, primary meningeal SMARCB1-deficient tumours have not been described. We report two cases of meningeal SMARCB1-deficient tumours occurring in adults. METHODS: We performed immunohistochemical analyses, comparative genomic hybridization, fluorescence in situ hybridization and targeted next-generation sequencing. RESULTS: The first meningeal tumour was a solitary mass, composed of rhabdoid, adenoid, chordoid and sarcomatoid areas. The second case presented as multiple, bilateral, supra and infratentorial nodules, was composed of fusiform and ovoid cells embedded in a myxoid stroma. Tumour cells were positive for epithelial membrane antigen (EMA), vimentin and CD34 and negative for SMARCB1 and meningothelial, melanocytic, muscular, glial markers. In the first case, one allele of SMARCB1 was completely deleted, whereas in the second case, loss of expression of SMARCB1 was observed as a consequence of a homozygous deletion of SMARCB1. CONCLUSIONS: The phenotype and genotype of these two cases did not fit diagnostically with entities already known to be SMARCB1-deficient tumours. As both tumours shared common features, they are regarded as belonging to an emerging group of primary meningeal SMARCB1-deficient tumours, not described to date. To facilitate the identification and characterization of these tumours, we recommend SMARCB1 immunohistochemistry for primary meningeal tumours which are difficult to classify, especially if immunopositive for EMA and CD34.

[Role of radiotherapy in the management of non-Hodgkin lymphomas]. / Place de la radiothérapie dans la prise en charge des lymphomes malins non hodgkiniens.

The purpose of this review was to summarize recent data about lastest retrospective and prospective studies dealing with radiotherapy of non-Hodgkin lymphoma, in order to precise the schedule and the role of this treatment. A systematic review was done by searching studies on the website http://www.pubmed.gov (Medline) using the following keywords: radiotherapy, radiation therapy, non-Hodgkin lymphoma. The management of non-Hodgkin lymphoma varies a lot according to the histological type and stage. The dose of radiotherapy has been studied in only one randomized trial, which concluded that there was no difference between the low dose and the high dose arms. Radiotherapy is a very good option in follicular, cutaneous, digestive or orbital non-Hodgkin lymphoma. A recent post hoc analysis of randomized trials on radiotherapy for high-grade non-Hodgkin lymphoma strongly suggested a benefit of additional radiotherapy after chemotherapy in some situations. Radiotherapy of low-grade non-Hodgkin lymphoma is a very good option, while its use on high-grade non-Hodgkin lymphoma is sometimes recommended but further randomized trials are ongoing to better understand its role.

[Malignant tumours of the eye: Epidemiology, diagnostic methods and radiotherapy]. / Tumeurs malignes ophtalmologiques : indications de la radiothérapie et techniques.

Malignant tumours of the eye are not common, barely representing 1 % of all cancers. This article aims to summarise, for each of the main eye malignant diseases, aspects of epidemiology, diagnostic methods and treatments, with a focus on radiation therapy techniques. The studied tumours are: eye metastasis, intraocular and ocular adnexal lymphomas, uveal melanomas, malignant tumours of the conjunctive, of the lids, and retinoblastomas. The last chapter outlines ocular complications of radiation therapy and their management.

Management of choroidal metastases.

BACKGROUND: Choroidal metastases (CM) are the most common malignant intraocular lesion observed in up to 4-12% of necropsy series of patients with solid cancer. The spectrum of presentations varies from prevalent CM in disseminated cancer to isolated CM. CM are responsible for visual deterioration. Depending on the primary cancer, estimated life expectancy, overall cancer presentation and ocular symptoms, the management of CM varies widely. We address the multidisciplinary management of CM and technical aspects of radiotherapy. MATERIAL AND METHODS: A systematic review of literature was performed from 1974 to 2014. RESULTS: Choroidal metastases occur preferentially in breast and lung carcinomas but are reported in all cancer types. The standard treatment remains external beam radiotherapy, applying 30Gy in 10 fractions or 40Gy in 20 fractions. The reported complete response and improved visual acuity rates are 80% and 57% to 89%, respectively. Some chemotherapy or new targeted therapy regimens yield promising CM response rates. DISCUSSION: Radiation therapy consistently shows rapid symptom alleviation, yield excellent local control and functional outcomes. However, there are only few reports on late toxicities after 6months given the unfavorable prognostic of CM patients. Selected patients may live more than two years, underlying the need to better assess mean and long term outcomes. Some authors have favored exclusive systemic strategies with omission of irradiation. The current literature suffers from the scarcity of prospective trials. Duration of tumor response following systemic therapy is rarely reported but appears less favorable as compared to radiotherapy. Systemic treatments may be proposed for pauci-symptomatic CM in a polymetastatic context while radiation therapy remains necessary in symptomatic CM either upfront or as an alternating treatment. Focalized radiation like brachytherapy and proton therapy may be proposed for isolated CM with long disease-free interval between primary and CM, as these techniques have the potential to yield better tumor and functional outcomes in patients with long life expectancy.

Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine.

Metaphase cytogenetics (MC) has a major role in the risk stratification of patients with myelodysplastic syndromes (MDSs) and can affect the choice of therapies. Azacitidine (AZA) has changed the outcome of patients with MDS or acute myeloid leukemia (AML) unfit for intensive chemotherapy. Identification of patients without the benefit of AZA would allow AZA combination or other drugs in first-line treatments. New whole-genome scanning technologies such as single nucleotide polymorphism microarray (SNP-A)-based molecular karyotyping (MK) improve the risk stratification in MDS and AML. Maintenance of genomic integrity is less than three megabases (Mbs) total disruption of the genome correlated with better overall survival (OS) in patients with lower-risk MDS. In this SNP-A study, we aimed at defining a cutoff value for total genomic copy number (CN) alterations (TGA) influencing the median OS in a cohort of 51 higher-risk MDS/AML patients treated with AZA. We observed that the relative risk of worse OS increased >100 Mb of TGA, as detected by SNP-A-based MK (8 and 15 months respectively, P=0.02). Our data suggest that precise measurement of TGA could provide predictive information in poor and very poor revised International Prognostic Scoring system (IPSS-R) patients treated with AZA.

Very Late Local Relapse of Ewing's Sarcoma of the Head and Neck treated with Aggressive Multimodal Therapy.

Ewing's sarcoma's relapse rarely occurs more than two years after the initial diagnosis. We report the case of a 26-year-old man with a history of Ewing's sarcoma of the left maxillary sinus at the age of 10 who presented with a very late local relapse, 16 years after the first occurrence of disease. Ultimate control was achieved after multimodal therapy including surgery, high-dose chemotherapy, and radiotherapy. This report indicates that local relapses of Ewing's sarcoma can be treated with curative intent in selected cases.