Primitive Tumor Research Articles

Évolution des oncocytomes rénaux surveillés

Oncocytomas are primitive kidney tumours, considered benign but their evolution is not fully established. The local progression is generally admitted but few data explain what makes a oncocytoma to grow more or less quickly. The objective of our study is to analyse the evolution of followed renal oncocytomas after histologic confirmation and to identify factors that can influence their growth. This is a retrospective study in two centers (North Hospital and Hospital of the Conception of Marseille). All patients with renal oncocytoma diagnosed with percutaneous biopsy from September 2010 to April 2016 and followed for more than one year were included. Epidemiological, histological, and morphological data were collected at diagnosis, during follow-up and in case of strategy change (intervention). Statistical analysis of factors influencing oncocytomes growth was based on the Pearson correlation test. Fifty-three patients were included. The median age for diagnosis was 65 years [39-85]. The sex ratio H/F was 6/5. The median follow-up was 34 months [12-180]. The average diagnosis size was 29 mm [12-90]. Thirteen patients (25%) were treated secondarily, including 70% by conservative treatment. The average growth was 0.25 (±0.23) cm/yr. The patients treated were younger and had a higher growth rate than the untreated (0.48±0.23cm/yr versus 0.18±0.18cm/yr, P<0,001). According to Pearson's analysis, there was a positive linear relationship (R=0.27, P=0.047) between velocity and initial size and a negative linear relationship (ρ=-0.44, P<0.001) between velocity and age at diagnosis. So tumor growth was faster if the patients were young and the tumor voluminous at diagnosis. Rapid growth often leads to a cessation of surveillance in favour of an intervention strategy. For young patients, conservative treatment (partiel nephrectomy or ablative treatment) in the medium term is likely to be preferred, but for elderly patients or with important comorbidities follow-up is an alternative to an invasive attitude. 3.

Effectiveness and safety in radiofrequency ablation of pulmonary metastases from HCC: a five years study.

Hepatocellular carcinoma (HCC) is a frequent tumor that may be treated with radiofrequency thermal ablation (RFA). RFA has been used with success also in treatment of pulmonary metastases from a wide range of primitive tumors, especially colorectal. Previous studies have shown that RFA con be used in treating HCC pulmonary metastases. Purpose of our study was a retrospective evaluation of overall survival and complication rates of percutaneous CT-guided radiofrequency ablation of pulmonary metastases from hepatocellular carcinoma (HCC). Data were collected from 40 CT-guided ablation sessions performed on 42 lesions in 26 patients (16M and 10 F; mean age 62.5years) with pulmonary metastases from HCC (size range 0.3-4cm, mean diameter 1.4 ± 0.98cm) from February 2012 to December 2017. All patients, as in advanced stage of illness (stage C), were treated according to Barcelona Clinic Liver Cancer (BCLC) criteria, with Sorafenib. They had no active HCC foci in the liver and no more than three metastases in the lung. Patients did not discontinue medical therapy with Sorafenib and pulmonary relapses were treated up to three times. In two patients two lesions were treated during the same procedure. Each lesion was ablated under CT guidance. Follow-up contrast-enhanced CT at 1, 3, 6, 12-month and every 6months after treatment were reviewed. A total of 42 metastatic lung lesions from HCC in 26 patients (57% male, 43% female) were treated with CT-guided radiofrequency thermal ablation procedures. Immediate radiofrequency ablation-related complications (subtle pneumothorax) were observed in 9 of 40 procedures (22.5%). Only one patient developed a pneumothorax requiring drainage tube insertion (2.5%). No other major complications occurred. Moreover, no significant worsening of pulmonary function was observed. In all patients the overall survival rates were 88.5% at 1year, 69.8% at 3years and 26.2% at 5years. Our retrospective assessment confirmed that percutaneous CT-guided radiofrequency thermal ablation in 23 patients with pulmonary metastases from HCC represents an effective and safe alternative treatment option in patients not considerable as potential candidates to surgery.

Gene of the month: BCOR

BCL-6 transcriptional corepressor (BCOR) gene is located at Xp11.4 and encodes a protein which is involved in transcriptional repression in association with BCL-6 and epigenetic silencing through polycomb repressive complex...

Primitive Myxoid Mesenchymal Tumor of Infancy in the Orbit: A New Location for a Rare Tumor.

Primitive myxoid mesenchymal tumor of infancy is a rare subtype of sarcoma. With the advent of relevant immunohistochemical and genetic analysis, it was defined by Alaggio et al. in a 2006 case series. Since then, 25 further cases are described in the literature-arising variably from the neck, chest, scalp, abdomen, back, or limbs. Here it is described for the first time arising in the orbit, confirmed by identification of BCOR immunopositivity with internal tandem duplication. All specialties involved in the management of orbital masses should be aware of the subtypes of sarcomas found in the orbit as approaches to their management may change depending on the diagnosis. As more cases are identified, a better understanding of this tumor's clinical behavior and appropriate management can be established.

Primitive Neuroectodermal Tumour of the Maxilla Sinistra Region

Primitive neuroectodermal tumors (PNET) are a group of malignant tumors composed of small round cells of neuroectodermal origin that affect soft tissue and bone. PNET have a rare incidence, occurring usualy in children and adolescents, rarely in adults. In this case report are focus of Peripheral primitive neuroektodermal tumors. Peripheral primitive neuroectodermal tumors (PNETp) are a group of aggressive malignancies that most commonly present in multiple tissues and organs including kidney, adrenal, bladder, liver, small intestine, colon and rectum, with a preferred location within the chest area (thoracopulmonary region), in the limbs and around the spine, but rarely, in the head and neck area. Here we present a case of the maxilla sinistra PNETp in a 17-year-old girl and we discuss the clinical features, histopathological characteristics, diagnosis, and treatment.

Hypoxia PET imaging beyond 18F-FMISO in patients with high-grade glioma: 18F-FAZA and other hypoxia radiotracers

High-grade gliomas are aggressive primitive brain tumors presenting aberrant vasculature, regional necrosis, and areas of hypoxia. Tumor hypoxia is associated with resistance to conventional treatment and worse prognosis. [18F]-fluoromisonidazole (18F-FMISO) is the most extensively investigated radiotracer for the evaluation of hypoxia. However, the use of 18F-FMISO in clinical practice has been hampered mainly due to the slow clearance of the unbound tracer from normoxic tissue and its low tumor-to-background ratio (TBR). The research community has therefore investigated other radiotracers to overcome the drawbacks of 18F-FMISO. This mini-review aims to present an update on the most relevant PET studies published in the last 15 years evaluating the utility of radiotracers for hypoxia imaging other than 18F-FMISO in high-grade glioma (HGG) patients. A comprehensive computer literature search of studies was carried out in PubMed/MEDLINE database to identify the most relevant studies published in the last 15 years which investigated the utility of hypoxia PET tracers other than 18F-FMISO in the assessment of tumor hypoxia in patients with HGG. 18F-flouroazomycin arabinoside (18F-FAZA) has been proposed as a valid alternative to 18F-FMISO for the assessment of hypoxia, due to its improved biodistribution and enhanced tumor-to-background ratio. Also 1-(2-[18F]fluoro-1[hydroxymethyl]ethoxy)methyl-2-nitroimidazole(18F-FRP170) seems a valuable hypoxia tracer in patients with brain tumor. The value of copper-diacetyl-bis(N4-methylthiosemicarbazone)(Cu-ATSM) seems controversial. Few evidences still exist regarding the utility of 18F-2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (18F-EF5). Hypoxia PET imaging has the potential to provide useful information for the clinicians and to guide hypoxia tailored treatments. According to the present literature, the most promising hypoxic tracer seems to be 18F-FAZA, but well-designed and wide trials to validate hypoxia radiotracers and evaluate their clinical utility in daily practice are still lacking.

Prostate cancer with low burden skeletal disease at diagnosis: outcome of concomitant radiotherapy on primary tumor and metastases.

To evaluate toxicity and clinical outcome in synchronous bone only oligometastatic (≤2 lesions) prostate cancer patients, simultaneously irradiated to prostate/prostatic bed, lymph nodes and bone metastases. From 2/2009 to 6/2015, 39 bone only prostate cancer patients underwent radiotherapy (RT) at "radical" doses to bone metastases (median 2 Gy equivalent dose, EQD2>40Gy, α/β = 1,5), nodes, and prostate/prostatic bed, within the same RT course, in association with androgen deprivation therapy (ADT).Biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were evaluated. After a median follow-up of 46.5 (1.2-103.6) months, 5 patients died from disease progression, 10 experienced biochemical relapse, 19, still in ADT, presented undetectable prostate-specific antigen (PSA) at the last follow-up. Five patients who discontinued ADT after a median of 34 months (5.8-41) are free from biochemical relapse.The 4 year Kaplan-Meier estimates of biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were 53.3%, 65.7%, 73.4% and 82.4% respectively.No Grade > 2 acute events and only two severe late urinary events were recorded, not due to the concomitant treatment of primary and metastatic disease. Our results suggest that "radical" and synchronous irradiation of primitive tumor and metastatic disease may be a valid approach in synchronous bone only prostate cancer patients, showing mild toxicity profile and promising survival results. To the best of our knowledge, this is the first analysis of clinical outcome in synchronous bone-only metastasis (neither nodal nor visceral) patients at diagnosis, treated with radical RT to all disease, associated to ADT.

Secondary Extra-anatomic Infrainguinal Bypass following Lower Limb Tumoral Resection

Soft tissue malignancy of lower limb can involve femoral triangle by direct tumoral invasion or secondary to ganglionic metastasis. Secondary arterial complications can appear during follow-up after initial tumoral resection and local radiation therapy. The aim of this study is to report our experience of secondary extra-anatomical lower limb revascularization following lower limb oncological resection with femoral bifurcation involvement. This is a retrospective monocentric study including patients who underwent extra-anatomical iliopopliteal bypass, with a previous treated neoplasia involving homolateral femoral bifurcation. Proximal anastomosis was performed on the iliac artery, tunnelization was made through iliac wing, and distal anastomosis was done on distal superficial femoral or popliteal artery. Five patients underwent extra-anatomic iliopopliteal bypass for oncological purpose from 2008 to 2018 at our institution. Mean age at surgery time was 52years (standard deviation=19.3). Prosthetic graft was used in all cases. Primitive tumor involved Scarpa triangle in 3 cases (soft tissue sarcomas) and ganglionic metastasis involved Scarpa triangle in 2 cases (epidermoid carcinoma). Clinical presentation was ischemic in 4 cases and hemorrhagic in 1 case. One patient died during hospitalization. Of the 4 survivors, 3 patients had a patent bypass at the end of follow-up (2 had bypass thrombectomy, 1 patient had major amputation). Secondary iliopopliteal bypasses through the iliac wing following lower limb tumoral resection have acceptable results. It is a valid option for limb salvage especially after local radiation therapy and tumoral resection. Multidisciplinary management is necessary to obtain acceptable results and follow-up is mandatory.

Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas: Molecular Characterization and Proposal for a Separate Classification.

Thyroid gland teratomas are rare tumors that span a wide clinicopathologic spectrum. Although benign and immature teratomas arise in infants and young children and generally have good outcomes, malignant teratomas affect adults and follow an aggressive course. This divergent behavior raises the possibility that benign/immature and malignant teratomas are separate entities rather than different grades of a single tumor. However, the histogenesis and molecular underpinnings of thyroid gland teratomas are poorly understood regardless of grade. In this study, we performed next-generation sequencing on 8 thyroid gland teratomas, including 4 malignant, 3 benign, and 1 immature. We identified DICER1 hotspot mutations in all 4 malignant cases (100%) but not in any benign/immature cases (0%). No clinically significant mutations in other genes were found in either group. We also performed immunohistochemistry to characterize the primitive components of malignant teratomas. Not only did all cases consistently contain immature neural elements (synaptophysin and INSM1 positive), but also spindled cells with rhabdomyoblastic differentiation (desmin and myogenin positive) and bland epithelial proliferations of thyroid follicular origin (TTF-1 and PAX8 positive). Although DICER1 mutations have previously been implicated in multinodular hyperplasia and well-differentiated thyroid carcinomas, these findings demonstrate the first recurrent role for DICER1 in primitive thyroid tumors. The combined neural, rhabdomyoblastic, and homologous epithelial elements highlighted in this series of malignant thyroid gland teratomas parallel the components of DICER1-mutated tumors in other organs. Overall, these molecular findings further expand the differences between benign/immature teratomas and malignant teratomas, supporting the classification of these tumors as separate entities.

P1248 What are the suspicious echocardiographic features of a malignant cardiac mass?

Abstract BACKGROUND Cardiac Masses (CM) represent a rare and heterogeneous group with a prevalence of 0.3% at autopsy, divided in benign masses - primary tumors and pseudotumors - and malignant ones - primitive tumors and metastasis, either directly invading the heart and pericardium or as a consequence of hematologic spread. 2-D Echocardiography is nowadays the first line approach to define nature and management of CM, but is it enough to guide a therapeutic strategy? PURPOSE To evaluate echocardiographic CM malignancy features in patients admitted to our Centre between 1997 and 2017. MATERIALS AND METHODS We retrospectively evaluated a population of 180 consecutive patients (45% males; mean age 60 ± 16 years; BMI 25 ± 5 Kg/m2), referred to our echocardiographic lab with suspicion CM. All patients were examined in both left lateral and supine position, and heart was visualized from all available echocardiographic windows. Definite diagnosis was obtained by histologic examination of biopsy, surgical samples or, in cases of cardiac thrombi, by radiological evidence of thrombus resolution after adequate anticoagulant treatment. We excluded normal anatomical variants in the group of pseudotumors due to the impossibility of obtaining histological examination. Comparisons between categorical variables were performed by Chi-square or Fisher exact test. P values ≤ 0.05 were considered significant. Variables with statistical signification lower than p ≤ 0.05 in univariable analysis were included in logistic regression analysis to determinate independent predictors of malignant masses. RESULTS We detected 129 benign CM (76% primitive tumors and 24% pseudotumors) and 51 malignant cardiac tumors (45% primitive tumors and 55% metastasis). In 7 cases a poor acoustic window did not allow an optimal examination; in remaining 173 patients, the classical 2-D echocardiogram identified 157 masses with a diagnostic accuracy of 91%. Benign tumors and pseudotumours were localized predominantly in left heart chambers, while malignant primitive tumors and metastasis were mainly detected in right heart, in pericardium or in pulmonary artery branches (p &amp;lt; 0.001). The largest ecocardiographic diameter appeared greater for the malignant masses (mean of 49 ± 26 mm) than benign ones (30 ± 16 mm, p = 0.003). The occurrance of any pericardial effusion (p &amp;lt; 0.001), extension to pericardium (p = 0.01) or to main vessels (p = 0.006) were also associated with malignant masses. Finally, multivariate analysis showed only largest diameter (p = 0.001) and pericardial effusion (p &amp;lt; 0.001) were independent predictors of malignancy. CONCLUSION 2D Echocardiography is an excellent, non invasive technique for first line evaluation of patients with suspicion CM. It is safe, accurate and have high diagnostic accuracy in identifying CM and their benign or malignant nature. In particular, a large mass associated with any pericardial effusion must pose suspect of malignancy.

Primitive Neuroectodermal Tumor of Cervix: Report of a Rare Case and Review of Literature

Background – Primitive neurocetodermal tumor / Ewing’s sarcoma (PNET/ES) of uterine cervix is extremely rare tumor and only 27 cases have so far been reported in the literature. We hereby present one case report diagnosed by histopathology and IHC and review of literature. Objective –A young girl aged 20 years was admitted. Her routine investigations and CT and MRI scan of chest, abdomen and pelvis were performed. Biopsy was taken from vaginal mass and histopathologist reported as round cell tumor. The slides were reviewed by another pathologist and found to be rhabdomyosarcoma. Thus immunohistopathology was done and a diagnosis of PNET/ES was established. Methods – The patient presented with complains of vaginal bleeding, generalized body ache, poor nutritional intake, found extensive loco regional disease with metastases to liver, lung and multiple bones, stage FIGO IV, performance score ECOG -4. Owing to her low general condition, we could not plan any anti-cancer treatment like chemotherapy or radiation therapy. She was discharged on symptomatic treatment. Results – Her biopsy and immunohistopathology turn out to be PNET/ES of uterine cervix. Conclusion - The rarity of this entity poses a challenge to pathologists and oncologists. The PNET/ES of uterine cervix can be potentially curable if presented at an early stage and found operable. IHC plays an important role in establishing this rare diagnosis.

P663 Is echocardiogram alone sufficient for cardiac masses characterization?

Abstract BACKGROUND Cardiac Masses (CM) represent an heterogeneous group with a prevalence of 0.3% at autopsy, divided in benign masses (primary tumors and pseudotumors) and malignant ones (primitive tumors and metastasis). 2-D Echocardiography is nowadays the first line approach to define nature and management of CM, but is it enough to guide a therapeutic strategy? PURPOSE To evaluate echocardiographic diagnosis accuracy for CM in patients admitted to our Centre between 1997 and 2017. MATERIALS AND METHODS We retrospectively evaluated a population of 180 consecutive patients (45% males; mean age 60 ± 16 years; BMI 25 ± 5 Kg/m2), referred to our echocardiographic lab with suspicion CM. All patients were examined in both left lateral and supine position, and heart was visualized from all available echocardiographic windows. Definite diagnosis was obtained by histologic examination of biopsy, surgical samples or, in cases of cardiac thrombi, by radiological evidence of thrombus resolution after adequate anticoagulant treatment. We excluded normal anatomical variants in the group of pseudotumors due to the impossibility of obtaining histological examination. Sensitivity, specificity, predictive accuracy for a positive test, and predictive accuracy for a negative test were calculated by standard formulas (corrected for prevalence by Bayes theorem). RESULTS We detected 129 benign CM and 51 malignant cardiac tumors. In 7 cases a poor acoustic window did not allow an optimal examination; in remaining 173 patients, the classical 2-D echocardiogram identified 157 masses with a diagnostic accuracy of 91%. Of 173 CM diagnosed, 146 were classified by echocardiographer as benign masses (125 true benign on histological examination) and 27 as malignant ones (all malignant after histological confirmation); the results showed 56% sensitivity, 100% specificity, 100% positive predictive value, 98% negative predictive value, with 88% overall diagnostic accuracy in identifying the nature of masses. 23 cases were undetermined and needed second level instrumental investigations to be characterized. Diagnostic accuracy for distinguishing primary benign tumors and pseudotumors decreased to 80%, with a significant increase in both "false" benign tumors (9 out of 91) and "false" pseudotumors (15 out of 34) with 85% sensitivity, 68% specificity, 10% positive predictive value, 99% negative predictive value. CONCLUSION 2D Echocardiography is an excellent, non invasive technique for first line evaluation of patients with suspicion CM. It is safe, reliable with a high predictive value and diagnostic accuracy in identifying CM and their benign or malignant nature. In contrast, these results were insufficient to start an anticoagulant in suspicion thrombus or cardiac surgery for primary tumor, since second level instrumental examinations needed. 2D Echocardiography alone seems unuseful for classifying malignant masses in primitive or metastasis.

Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells

ABSTRACT Cytokine-Induced Killer (CIK) cells share several functional and phenotypical properties of both T and natural killer (NK) cells. They represent an attractive approach for cell-based immunotherapy, as they do not require antigen-specific priming for tumor cell recognition, and can be rapidly expanded in vitro. Their relevant expression of FcγRIIIa (CD16a) can be exploited in combination with clinical-grade monoclonal antibodies (mAbs) to redirect their lytic activity in an antigen-specific manner. Here, we report the efficacy of this combined approach against triple negative breast cancer (TNBC), an aggressive tumor that still requires therapeutic options. Different primitive and metastatic TNBC cancer mouse models were established in NSG mice, either by implanting patient-derived TNBC samples or injecting MDA-MB-231 cells orthotopically or intravenously. The combined treatment consisted in the repeated intratumoral or intravenous injection of CIK cells and cetuximab. Tumor growth and metastasis were monitored by bioluminescence or immunohistochemistry, and survival was recorded. CIK cells plus cetuximab significantly restrained primitive tumor growth in mice, either in patient-derived tumor xenografts or MDA-MB-231 cell line models. Moreover, this approach almost completely abolished metastasis spreading and dramatically improved survival. The antigen-specific mAb favored tumor and metastasis tissue infiltration by CIK cells, and led to an enrichment of the CD16a+ subset. Data highlight the potentiality of this novel immunotherapy strategy where a nonspecific cytotoxic cell population can be converted into tumor-specific effectors with clinical-grade antibodies, thus providing not only a therapeutic option for TNBC but also a valid alternative to more complex approaches based on chimeric antigen receptor-engineered cells. List of abbreviations ACT, Adoptive Cell Transfer; ADCC, Antibody-Dependent Cell-mediated Cytotoxicity; ADP, Adenosine diphosphate; BLI, Bioluminescence Imaging; CAR, Chimeric Antigen Receptor; CIK, Cytokine Induced Killer cells; CTX, Cetuximab; DMEM, Dulbecco’s Modified Eagle Medium; EGFR, Human Epidermal Growth Factor 1; ER, Estrogen; FBS, Fetal Bovine Serum; FFPE, Formalin-Fixed Paraffin-Embedded; GMP, Good Manufacturing Practices; GVHD, Graft Versus Host Disease; HER2, Human Epidermal Growth Factor 2; HRP, Horseradish Peroxidase; IFN-γ, Interferon-γ; IHC, Immunohistochemistry; IL-2, Interleukin-2; ISO, Irrelevant antibody; i.t., intratumoral; i.v., intravenous, mAbs, Monoclonal Antibodies; mIHC, Multiplex Fluorescence Immunohistochemistry; MHC, Major Histocompatibility Complex; NK, Natural Killer; NKG2D, Natural-Killer group 2 member D; NSG, NOD/SCID common γ chain knockout; PARP, Poly ADP-ribose polymerase; PBMCs, Peripheral Blood Mononuclear Cells; PBS, Phosphate-buffered saline; PDX, Patient-derived xenograft; PR, Progesterone; rhIFN-γ, Recombinant Human Interferon-γ; RPMI, Roswell Park Memorial Institute; STR, Short tandem Repeat; TCR, T Cell Receptor; TNBC, Triple Negative Breast Cancer; TSA, Tyramide Signal Amplification

CENTRAL NECESSITY HEPATECTOMY FOR SPONTANEOUS RUPTURE OF HEPATOCELLULAR CARCINOMA AT A PATIENT WITH PORTAL BIFURCATION THROMBOSIS

Hepatocellular carcinoma (HCC), one of the commonest primitive malignant tumors of the liver, is currently considered one of the very high life-threatening tumors. Surgery remains the treatment of choice of HCC and is indicated whenever possible. We present the case of a patient 66 years old , at which abdominal CT scan reveals the presence of HCC in segments 4 and 8, broken, and perisplenic and perihepatic fluid accumulation in the context of declining hemoglobin. Associate there is an incomplete picture of the portal convergence of 1.9 cm, with the lack of visualization of the left portal wreath. Even in the absence of the possibility of curative resection due to spontaneous rupture of the liver tumor, it is made a central necessity hepatectomy and subsegmentectomy 2 and 3 for the other three formations located at this level. Patient's postoperative course was favorable and he was discharged 11 days after surgery. Abdominal MRI performed 2 months postoperatively revealed the presence of multifocal recurrence. Patient dies at 6 months postoperatively.

AGGRESSIVE PRIMITIVE TUMOR IN A PEDIATRIC PATIENT WITH LETHAL EVOLUTION

Primitive tumors are considered rare, malignant, small and round-cell tumors that represent a disease of childhood and categorized into the Ewing family of tumors due its similarities. Herein we report a case of primitive tumor in a pediatric patient with lethal evolution. A 1-year-old black male patient was showing an expansive lesion in the left hemimandible, 8 cm in diameter, exhibiting superficial telangiectasia, crackling consistency, similar to a mucous membrane. The radiographic findings revealed irregular lytic radiolucency. An incisional biopsy was performed and the histopathologic report suggested a mucoepidermoid carcinoma. A histochemical and immunohistochemical panel was performed with the following markers: PAS-stain (+), DAK-p63 (+), AE1 ⁄AE3 (+), S-100 (+), and calponin (focaly +). The patient died 2 months after the biopsy procedure, before the immunohistochemical report was finished. We discuss the aggressive nature of such a rare tumor.

A rare case of primary extra-osseous Ewing’s sarcoma presenting in the posterior neck

Ewing sarcoma is classified as Ewing’s sarcoma of the bone tissue, extraskeletal Ewing’s sarcoma, peripheral primitive neuroendocrine tumor, malignant small cell tumor of the thoracopulmonary region (Askin) and non-typical Ewing’s sarcoma. Extraosseous Ewing’s sarcoma may be seen throughout the body, however only reported at 4% in the neck. In our case patient has a painless mass growing on his posterior neck for 3 months.On the magnetic resonance imaging, a well-defined, encapsulated, well-demarcated mass lesion between the perivertebral muscles and the subcutaneus fat tissue was detected. Tumor was surgically resected and diagnosis was pathologically Ewing’s sarcoma. 22q11 translocation was detected in the molecular examination. Extraosseous Ewing sarcomas are rarely seen soft tissue masses. Although imaging features are not sufficient to make a specific diagnosis, it is important take the biopsy from the appropriate place and staging the tumor. In addition, complete surgical resection has been shown to associated with better survival rates compared to other Ewing sarcoma family. For this reason, imaging has an important role in the guidance of surgery and resectability of the tumor. Young patients with a fast growing, palpable mass should be evaluated carefully. Although the tumor is thought to be morphologically benign in the first, ekstraosseous Ewing’s sarcoma must be considered in the differential diagnosis of head and neck soft tissue masses.

Pancreatic resections for metastases: A twenty-year experience from a tertiary care center

BackgroundLiterature data about pancreatic resections for metastases are limited to small series, so that the role of surgery in this setting remains unclear. We herein report our experience from a tertiary care center, analyzing the outcomes of patients who underwent pancreatic resections for metastases and discussing the role of surgical resection in their management. Materials and methodsFrom January 1999 to January 2019, 26 patients underwent pancreatic resections for metastases from renal cell carcinoma (RCC-group) or other primitive tumors (non-RCC-group). Details regarding pre-, intra-, post-operative course, and follow-up, prospectively collected in a database of pancreatic resection, were retrospectively analyzed and compared. ResultsRCC-group was composed of 21 patients, non-RCC-group of 5 patients. RCC-group presented a longer disease-free interval: 96.4 vs. 5.4 months (p < 0.001). In 9/21 patients (42.9%) of RCC-group the surgical resection of other organs or vascular structures was performed, while in non-RCC-group pancreatic resection alone was performed in all cases, p = 0.070. No local recurrence was reported in all cases. The systemic recurrence rate was 42.9% (9/21 patients) in RCC-group and 80% (4/5 patients) in non-RCC-group, p = 0.135. RCC-group presented a longer DFS and OS: 107.5 vs. 25.2 months (p = 0.002), and 109.1 vs. 36.2 months (p = 0.016), respectively. ConclusionsRadical pancreatic resection may confer a survival benefit for RCC metastases, while for other primitive tumors it should be applied more selectively. For RCC pancreatic metastases, an aggressive surgical approach, even in patient with locally advanced tumors, or associated extra-pancreatic localizations, or recurrent metastases should be taken in consideration.

INNV-14. ADJUVANT CHEMOTHERAPY AFTER SEVERE MYELOTOXICITY DURING TEMOZOLOMIDE CHEMORADIATION IN GLIOMAS. IT IS FEASIBILE?

Abstract INTRODUCTION Malignant gliomas are aggressive primitive brain tumor in adults. Today, the standard of care is Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ. TMZ treatment has been considered to have a low toxicity profile. However, during concomitant treatment some patient may develop a severe myelosuppression. This toxicity may be in some cases prolonged and lead to treatment discontinuation. METHODS We have retrospectively collected data from 5 Italian neuro-oncological centers, about glioma patients who developed severe and prolonged hematological toxicity during concomitant chemoradiotherapy with TMZ. The purpose of this study is to evaluate: percentage of patients receiving adjuvant chemotherapy after severe myelotoxicity; rate of toxicity observed during adjuvant chemotherapy. RESULTS 54 glioma patients who developed myelosuppression of grade 3 or 4 were considered. Histology was Glioblastoma in 45 patients (83%); 63% of patients were female. Myelotoxicity during concomitant phase occurred at a median of 4 weeks (range 1–8) from the start of treatment. After recovery of myelotoxicity 19 patients did not received any treatment while 35 (65%) were treated with chemotherapy (28 received standard TMZ, one TMZ with metronomic schedule, 2 lomustine and 4 other agents). Among patients treated with TMZ, 13 patients presented hematological toxicity grade 3–4 which required treatment discontinuation in 7 cases (20%). CONCLUSION the results of our study show that 80% of glioma patients presenting severe myelotoxicity during concomitant radiochemotherapy may be treated with maintenance TMZ after recovery of myelosuppression.

P11.06 Non epigenetic effect of vorinostat in glioblastoma cells

Abstract BACKGROUND Glioblastoma multiform (GBM) is the most frequent primitive brain tumor. GBM has a high recurrence and mortality. Histone deacetylase (HDAC) inhibitors have evoked great interest because they are able to change transcriptomic profiles to promote tumor cell death but also show undesirable side effects due to the lack of selectivity.We show new properties of low dose vorinostat, which inhibits cytoplasmic HDAC6 and display interesting non-epigenetics effects, especially on the microtubular cytoskeleton. MATERIAL AND METHODS We used murine (GL261) and human (U87 and GBM6 stem cells) cellular models. The cell proliferation was assessed by MTT tests, the migration by the 24 hours Transwell technic and by wound/healing tests. The expression levels of proteins of interest were assessed by Western Blot. Microtubules dynamics were assessed by time-lapse videomicroscopy. The synergy between drugs was tested by Loewe model. RESULTS Vorinostat inhibited the proliferation and the migration of the three cell lines mentioned above at level below the EC50.Vorinostat induces tubulin acetylation and alpha-tubulin c-terminal detyrosination that signed microtubular stabilization and these effects are independent of histone acetylation (HADC3). Interestingly, vorinostat decreases EB1 expression (a bad prognostic factor in GBM) and decreases microtubule dynamics. Moreover, vorinostat decreases neural markers such as GFAP, beta3-tubulin and CNPase and increases mural markers expression such as SMA/EGFR and PDGFR. Finally, it showed a synergy combined with erlotinib. CONCLUSION Low dose vorinostat, which do not affect histone désacetylase, has antitumor effect on glioblastoma cells by a new mechanism involving microtubule cytoskeleton. Interestingly, combination of low doses vorinostatand erlotinibshowed a strong synergy. Low dose, vorinostat could therefore represent an interesting therapeutic option and fewer side effects and that could be used to increased GBM patient sensitivity to erlotinib.

P14.83 Adjuvant chemotherapy after severe myelotoxicity during temozolomide chemoradiation in gliomas. It is feasibile? The talian Multicentric Study (AINO)

Abstract BACKGROUND Malignant gliomas are aggressive primitive brain tumor in adults. Today, the standard of care is Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ. TMZ treatment has been considered to have a low toxicity profile. However, during concomitant treatment some patient may develop a severe myelosuppression. This toxicity may be in some cases prolonged and lead to treatment discontinuation. MATERIAL AND METHODS We have retrospectively collected data from 5 italian neuro-oncological centers, about glioma patients who developed severe and prolonged hematological toxicity during concomitant chemoradiotherapy with TMZ. The purpouse of this study is to evaluate: percentage of patients receiving adjuvant chemotherapy after severe myelotoxicity; rate of toxicity observed during adjuvant chemotherapy. RESULTS 54 glioma patients who developed myelosuppression of grade 3 or 4 were considered. Hystology was Glioblastoma in 45 patients (83%); 63% of patients were female. Myelotoxicity during concomitant phase occurred at a median of 4 weeks (range 1–8) from the start of treatment.After recovery of myelotoxicity 19 patients did not received any treatment while 35 (65%) were treated with chemotherapy (28 received standard TMZ, one TMZ with metronomic schedule, 2 lomustine and 4 other agents). Among patients treated with TMZ, 13 patients presented hematological toxicity grade 3–4 which required treatment discontinuation in 7 cases (20%). CONCLUSION we observed that 80 % of glioma patients presenting severe myelotoxicity during concomitant radiochemotherapy may be treated with maintenance TMZ after blood value recovery.