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Background An intrathoracic mass persists aftercompletion of treatment in 20% of the patients treated for Hodgkin'sdisease (HD) or non-Hodgkin's lymphoma (NHL). Gallium scan andpositron emission tomography allow for diagnosis in most cases. However, in some patients, a pathologic examination of the residualmass (RM) is required. The aim of this study was to evaluate theresults of a thoracoscopic approach for intrathoracic RM, as comparedwith image-guided biopsies. Patients and methods From1996 to 1998, 29 consecutive patients treated for NLH (n = 11) or HD(n = 18) were referred either to radiology (group R; n = 8) or tosurgery (group S; n = 21) for biopsy of an intrathoracic RM. Therewere 13 male and 16 female patients ranging in age from 15 to 56 years(mean, 32 years). The reason for a biopsy was the inability todetermine the nature of the RM by means of radiologic examination orscintigraphy. Biopsy was defined as successful when (1) residuallymphoma was found in the specimen, or (2) benign tissue was found andthe patient remained disease-free after a minimal follow-up period of12 months. A biopsy was defined as a failure when a local recurrenceoccurred in a patient with a diagnosis of benign lesion. Results No significant procedure-related complicationsoccurred in either group. The mean follow-up was 26 months (range, 13to 72 months). In group R, residual lymphoma was found in only onepatient. In group S, residual lymphoma was found in seven patients(p = 0.5). In the seven patients of group R with a diagnosis ofbenign mediastinal lesion, two patients had a local recurrence and onehad a recurrence within the abdomen. In the 15 patients of group S inwhom no residual disease was found, 1 patient had an intrathoracicrecurrence (p = 0.5) while 2 patients had recurrence in a remotesite. Conclusion Despite the limited number ofpatients in this series, results suggest that a thoracoscopic approachyields better data than image-guided biopsies.

BACKGROUND The prognostic impact of large mediastinal involvement (mediastinum/thorax [M/T] ratio > 0.33) in advanced Hodgkin disease (HD) and the optimal treatment with chemotherapy or combined treatment remains controversial. METHODS Among 533 assessable patients with Ann Arbor Stage IIIB/IV HD included in the H89 trial, 82 had large mediastinal mass defined on chest X-ray. All patients received induction with six cycles of chemotherapy (mechlorethamine, vincristine, procarbazine, prednisone–doxorubicin, bleomycin, vinblastine or doxorubicin, vinblastine, bleomycin, procarbazine, prednisone); then complete and good partial responders were randomized between two consolidation treatments: 2 cycles of the same chemotherapy or (sub)total lymph node irradiation. RESULTS Among 82 patients with an M/T ratio greater than 0.33, 48 were very large (ratio > 0.45). A large mediastinal mass was associated with supradiaphragmatic disease, younger age, histologic nodular sclerosis, and different sex ratio compared with other H89 trial patients. Biologic parameters and prognostic factors were similar for both groups. Although the major response rate to induction chemotherapy (after 6 cycles) was lower for patients with large mediastinal mass (78% vs. 86%), the 5-year overall survival rate (80% vs. 79%) and event free survival rate (59% vs. 61%) were similar (P = 0.64 and 0.3, respectively). The outcome was the same for patients (74%) with a large mediastinal mass randomized to 1 of the 2 consolidation arms. Analysis of progression showed that 68% (21 of 31) of failures occurred early during treatment and involved the mediastinum in 86% of the cases. CONCLUSIONS For patients with large mediastinal mass and advanced HD who achieved a major response of at least 75% after 6 cycles of chemotherapy, a consolidation radiation therapy can be replaced by 2 additional cycles of chemotherapy. Cancer 2001;92:453–9. © 2001 American Cancer Society.

Accumulation of visceral adipose tissue is associated with metabolic complications such as noninsulin-dependent diabetes mellitus. The aim of this study was to evaluate the effect of abdominal adipose tissue on insulin sensitivity in subjects with noninsulin-dependent diabetes mellitus (NIDDM). Areas of abdominal fat were calculated from axial magnetic resonance images obtained at the level of the umbilicus in 21 men with NIDDM [age, 45.6 +/- 8.3 (+/-SD) yr; body mass index, 29.3 +/- 4.5 kg/m(-2); total body fat (skinfold thickness), 26.8 +/- 5.4%; waist to hip ratio, 0.97 +/- 0.07; duration of diabetes, 59 +/- 47 months; hemoglobin A1c, 8.1 +/- 1.5%]. Insulin sensitivity was evaluated by an insulin tolerance test. The areas of deep abdominal fat and sc abdominal fat were, respectively, 135.3 +/- 55.1 and 211.8 +/- 99.1 cm2. The blood glucose disappearance rate was 2.11 +/- 0.87%/min and was negatively related to deep abdominal fat (r = 0.72; P = 0.0025). In contrast, areas of sc abdominal fat, total body fat, body mass index, and waist to hip ratio were not related to the blood glucose disappearance rate. Plasma triglyceride concentrations averaged 1.8 +/- 0.8 mmol/L and were positively related to deep abdominal fat (r = 0.69; P = 0.0018). We conclude that insulin sensitivity is strongly related to visceral adipose tissue accumulation in NIDDM.

The management of prostate cancer has dramatically changed due to the progresses made in imaging, especially in MRI. MRI in indicated in the initial workup of a patient with a biopsy proven prostate carcinoma eligible to a curative treatment. Detection MRI is used in patients with increased PSA levels and negative biopsies for targeting a new series of biopsies. Lastly, MRI combined with PET allows one to schedule a salvation treatment in patients with a biological relapse of prostate cancer after treatment and a local recurrence.

Background. L-asparaginase (L-ASPA) based-chemotherapy (chemo) is one of the most efficient treatment for patients with extra-nodal NK/T nasal type lymphoma, in front- line or at relapse. This treatment is combined either with radiation therapy (RT) if localized or with high dose therapy plus autologous stem cell transplantation (HDT/ASCT) if disseminated. However it may be associated with toxicities that may impair efficacy and survival. Aim. The aim of this study was to report the real-life experience of L-asparaginase use in patients with NK/T nasal type lymphoma treated with L-ASPA based-chemotherapy and to identify risk factors associated with 1/ main adverse events and 2/ survivals. Patients and methods. Between July 2003 and June 2016, 28 patients were treated in our center for NK/T nasal type lymphoma. Four of them were excluded because they did not receive L-ASPA- based chemotherapy. Among the 24 pts included, 21 received the L-ASPA based-chemo as front-line therapy, and 3 pts as second line, either in association with gemzar and dexamethasone (n=14), or with methotrexate and dexamethasone (n=6), or with etoposide and dexamethasone (n=1). RT was delivered in 18 pts; HDT/ASCT in 3 pts; and both in 1 pt. Median number of injections of L-ASPA was 12 per patient (range 3-32). Grade 3-4 of toxicities (tox) were retrospectively assessed according to CTCAE V4.03, with a particular attention to 4 categories: hematological, hemostasis, liver and pancreatic dysfunctions. Progression-free (PFS) and overall survivals (OS) were analyzed from time of first L-ASPA injection, based on Kaplan Meier estimates. Results. Median age at diagnosis was 51 years (interquartile range, IQR : 40.7-61, ranging from 24-78). Sex ratio M/F was 0.71. PS was > 2 in 3 patients. Median body mass index (BMI) was 24 kg/m 2 (IQR: 23-25.7, ranging from 17-33). Stage was localized in nasal site in 20 patients, and disseminated (III-IV) in 4 patients, with bone marrow involvement in 2 pts, muscle in 1 pt, skin in 1 pt, and extensive nasal in 1 pt. LDH level was high in 10 (41.7%) patients. At diagnosis, EBV serum DNA was positive in 15/20 (75%) patients. All patients were negative for HBV, HIV, HCV. Abnormal baseline levels of ASAT/ ALAT (> 2N) were present in 2 patients, amylase/lipase (>1.5N) in 2 pts, bilirubine (2N) in 4 pts. Baseline anemia (< 10g/L) and thrombopenia (< 100 G/L) were present in 6 and 2 patients, respectively. Hemostastic parameters were normal in all patients. During the treatment, 10 (42%) patients developed gr3-4 hepatic toxicities, and 3 (13%) pts pancreatic toxicities, 6 (25%) pts hematologic toxicities, 3 (13%) pts hemostatic toxicities. These toxicities induced a reduction of treatment in 6 (25%) patients. Hematological toxicities were associated to baseline hemoglobin and platelets levels and to poor PS (p= 0.008; p= 0.014 ; p= 0.095, respectively). Hemostatic toxicities were associated to the stage of the disease, but not significantly (p= 0.076). No factor was associated for hepatic or pancreatic toxicities. Age and BMI were not significantly associated to any toxicity. A complete remission was achieved at the end of treatment in 12 patients (50%). At 2 years, progression- free survival and overall survival were 39% (95%CI, 20.3-76%) and 51.5% (95%CI, 30-89%), respectively. Presence of toxicities impacted the progression free survival and overall survival, though not significantly (p= 0.0635 ; p= 0.0737) (Figure 1) Conclusion. In this small retrospective analysis, we observed an impact of toxicities related to L-ASPA on the PFS and the OS of patients with extra-nodal NK/T lymphoma. The identification of the risk factors associated to these toxicities needs to analyze large cohorts of prospective trials. Figure 1 Figure 1. Disclosures Brice: Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Seattle Genetics: Research Funding; Roche: Honoraria; Gilead: Honoraria; Bristol Myers-Squibb: Honoraria. Thieblemont:Roche: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees.

In patients with the Zollinger-Ellison syndrome, which is either sporadic or integrated into multiple endocrine neoplasia type 1, accurate localization of all the tumours is difficult and may have therapeutic implications. In an attempt to improve this localization, somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]-octreotide was performed prospectively in 48 consecutive patients with the Zollinger-Ellison syndrome. Thirty of them had the sporadic type of this disease. Scintigraphic data were compared with data obtained by conventional imaging methods, and also, in 32 selected patients, with those obtained by endoscopic ultrasonography. Somatostatin receptor scintigraphy showed abnormal tracer uptake in 39 patients (81%), in whom it correctly identified 50 of the 60 tumoral sites (83%) previously localized by the other imaging methods. In 17 patients (35%) somatostatin receptor scintigraphy disclosed abnormal tracer uptake at 18 different tumoral sites: 14 were located in the abdomen, including four in the liver and eight in the duodenopancreatic area, and four outside the abdomen, including two in the mediastinum. Six of the ten tumoral sites which were not correctly identified by somatostatin receptor scintigraphy were located in the duodeno-pancreatic area. However, in the 20 patients for whom conventional techniques failed to visualize any tumour in the duodenopancreatic area, somatostatin receptor scintigraphy was positive in ten (50%) whereas endoscopic ultrasonography was only positive in five (25%). In our patients with the Zollinger-Ellison syndrome, somatostatin receptor scintigraphy appeared to be a useful new addition to the battery of tests used for tumour detection.

Background To illustrate that Breast-MRI performed in high spatial resolution and low temporal resolution (1 minute) allows the measurement of kinetic parameters that can assess the final pathologic response to neoadjuvant chemotherapy in breast cancer. Methods Breast-MRI was performed in 24 women before and after treatment. Eight series of 1.11 minute-duration were acquired with a sub-millimeter spatial resolution. Transfer constant (Ktrans) and leakage space (Ve) were calculated using measured and theoretical Arterial Input Function (AIF). Changes in kinetic parameters after treatment obtained with both AIFs were compared with final pathologic response graded in non-responder (< 50% therapeutic effect), partial-responder (> 50% therapeutic effect) and complete responder. Accuracies to identify non-responders were compared with receiver operating characteristic curves. Results With measured-AIF, changes in kinetic parameters measured after treatment were in agreement with the final pathological response. Changes in Ve and Ktrans were significantly different between non-(N = 11), partial-(N = 7), and complete (N = 6) responders, (P = 0.0092 and P = 0.0398 respectively). A decrease in Ve of more than -72% and more than -84% for Ktrans resulted in 73% sensitivity for identifying non-responders (specificity 92% and 77% respectively). A decrease in Ve of more than -87% helped to identify complete responders (Sensitivity 89%, Specificity 83%). With theoretical-AIF, changes in kinetic parameters had lower accuracy. Conclusion There is a good agreement between pathological findings and changes in kinetic parameters obtained with breast-MRI in high spatial and low temporal resolution when measured-AIF is used. Further studies are necessary to confirm whether MRI contrast kinetic parameters can be used earlier as a response predictor to neoadjuvant chemotherapy.

Around 20% of Hodgkin lymphoma (HL) patients are refractory to first-line therapy with ABVD (adriamycin-bleomycin-vinblastine-dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose-reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide-etoposide-oxaliplatin) salvage regimen in terms of response rate, toxicity and stem-cell mobilization. Thirty-four patients with relapsed/refractory HL after anthracycline-containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m(2) days 1-3), etoposide (150 mg/m(2) days 1-3) and oxaliplatin (130 mg/m(2) day 1). Patients65 years old received high-dose therapy followed by autologous stem-cell transplantation (HDT-ASCT). Response was assessed by computed and positron-emission tomographies. Overall and complete response rates were 76% and 32%, respectively, after 2 cycles. Three episodes of febrile neutropenia occurred, and three patients required dose-reductions. Twenty-six patients underwent HDT-ASCT. With median follow-up at 5 years, the 5-year overall and event-free survival rates were 74% and 63%, respectively. IVOx is a well-tolerated outpatient regimen for relapsed HL, that does not hamper stem-cell mobilization, achieves good response rates and compares favourably with previously published salvage regimens.

Image-guided percutaneous transthoracic needle biopsy of the lung is a well-established method for the histological diagnosis of pulmonary lesions. The purpose of this review is to describe the different technical modalities including the biopsy procedures and sample conditioning methods. The main complications and the influence of various variables on the complication rate are discussed. The accuracy and sensitivity of this diagnostic method are reported with emphasis on patients with suspected malignancy and/or infection. These data are useful for predicting the risk of complications before the procedure and, therefore, for helping to select those patients most likely to benefit.

Aims: The treatment of dermatofibrosarcoma protuberans (DFSP) involves wide local excision with frequent need for reconstructive surgery. A t(17;22) translocation resulting in COL1A1-PDGFB fusion is present in >95% of cases. Certain patient observations and a report on nine patients suggest that imatinib mesylate, targeting platelet-derived growth factor receptor β, has clinical potential in DFSP. The primary aim of this phase II multicenter study was to define the percentage of clinical responders (Response Evaluation Criteria in Solid Tumors) to a 2-month preoperative daily administration of 600 mg of imatinib mesylate before wide local excision. The secondary aims were to determine tolerance, objective response from imaging results (ultrasound and magnetic resonance imaging), and pathologic responses observed in sequential tissue specimens. Patients and Methods: A two-stage flexible design was used with interim analysis after the recruitment of six patients. Twenty-five adults suffering from primary or recurrent DFSP were included from July 2004 to May 2006. Results: The COL1A1-PDGFB fusion gene was detected in 21 out of 25 patients following fluorescence in situ hybridization analysis (two cases were noninformative). A clinical response was achieved in nine (36%) patients (95% confidence interval, 18.9-57.5). The median relative tumoral decrease was 20.0% (range, −12.5 to 100). Apart from expected grade 1 or 2 side effects, we observed one grade 3 neutropenia, one grade 3 maculopapular rash, and one grade 4 transient transaminitis. Conclusion: Our results support the use of imatinib in a neoadjuvant setting in nonresectable DFSP, or when surgery is difficult or mutilating. These results will be useful for setting hypotheses in the evaluation of new drugs to treat primary or secondary resistance to imatinib. Clin Cancer Res; 16(12); 3288–95. ©2010 AACR.

Accurate staging of Hodgkin's lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow. (18)F-FDG PET/CT is now widely used for assessing response to therapy in HL and a baseline study is obtained to improve accuracy. The aim of this retrospective analysis was to assess whether routine BMB remains necessary with concomitant (18)F-FDG PET/CT.Data from 83 patients (newly diagnosed HL) were reviewed. All patients had received contrast-enhanced CT, BMB and (18)F-FDG PET/CT. Results of BMB were not available at the time of (18)F-FDG PET/CT imaging.Seven patients had lymphomatous involvement on BMB. Four patients had bone involvement on conventional CT (two with negative BMB). All patients with bone marrow and/or bone lesions at conventional staging were also diagnosed on (18)F-FDG PET/CT scan. PET/CT depicted FDG-avid bone/bone marrow foci in nine additional patients. Four of them had only one or two foci, while the other had multiple foci. However, the iliac crest, site of the BMB, was not involved on (18)F-FDG PET/CT. Osteolytic/sclerotic lesions matching FDG-avid foci were visible on the CT part of PET/CT in three patients. MRI ordered in three other patients suggested bone marrow involvement. Interim and/or end-therapy (18)F-FDG PET/CT documented response of FDG-avid bone/bone marrow foci to chemotherapy in every patient.(18)F-FDG PET/CT highly improves sensitivity for diagnosis of bone/bone marrow lesions in HL compared to conventional staging.

BACKGROUND The purpose of our study was to study the relevance of a systematic aorto-femoral colour Doppler ultrasound (DUS) in the evaluation of first renal transplant receivers. METHODS We prospectively studied 100 consecutive first renal transplant (RT) receivers. All patients had a preoperative physical examination with a careful vascular system evaluation including assessment of risk factors and colour DUS of aortic, iliac and femoral arteries. Renal transplantation was planned in the right iliac fossa with end-to-lateral vascular anastomoses. Clinical parameters, DUS results, operative and post-operative parameters at 3 months were compared according to the vascular assessment. RESULTS Among the 84 patients presenting with a normal preoperative physical arterial examination, 12 patients (14.3%) had an abnormal DUS, revealing atherosclerotic arteries, but no case of arterial stenosis. Among the 16 patients with abnormal physical arterial examination, 10 patients (62.5%) had abnormal DUS, including 4 cases of iliac stenosis. In 3 of the 16 patients (18.8%), DUS revealed right iliac artery stenosis requiring a modification in the surgical procedure. No additional vascular procedure was reported in the case of normal preoperative vascular examination. No technical problems during arterial anastomosis and no post-transplantation arterial complications were reported. In multivariate analysis, abnormal physical examination was the most significant risk factor of atherosclerotic infiltration in DUS. CONCLUSION The abnormality of arterial physical examination is the best clinical predictor of abnormal DUS in preoperative assessment of renal transplant receivers. However, the low sensitivity and positive predictive value of the physical examination do not support the conclusion that DUS can be avoided in patients with normal arterial physical examination. Nevertheless, in the case of arterial physical abnormality, 'for case' DUS is critical and helps in the surgical strategy in approximately 20% of cases.

International audience; Trichoderma longibrachiatum, a filamentous fungus, was recently described as an emerging pathogen in immunocompromised patients. Here, we report the first case, to our knowledge, of isolated invasive lung infection by T. longibrachiatum in a patient with hematologic malignancy. The infection mimicked invasive pulmonary aspergillosis and was successfully treated with a combination of voriconazole and caspofungin.

23 Background: In our institution, as soon as biochemical relapse (BR; nadir PSA + 2 ng/ml) occurred after external beam radiotherapy (EBRT) or brachytherapy (BT), 18-fluorocholine-PET-CT (18-FCH-PET) with or without multiparametric prostate MRI are performed. The aim is to select patients for a salvage local treatment (SLT) with a curative intent. We presented here the results of this approach. Methods: Records of patients with BR, without clinical evidence of relapsing disease and with at least a18-FCH-PET performed, were retrospectively reviewed. Patients were considered eligible for SLT if the relapse was only local or in case of nodal relapse reasonably encompass in a RT field. Results: Between 2010 and 2014, 89 pts were included, 23 initially treated with BT and 66 with EBRT. Prognostic group at diagnosis were: favourable: 25 (28%), intermediate: 35 (39%), unfavourable: 29 (33%). At the time of relapse, mean age was 72 yrs and mean PSA level: 6.2 ng/ml. After 18-FCH-PET ± MRI, patients were classified as: no target lesion identified: 20 (22.5%); local relapse: 35 (39%); nodal relapse: 22 (25%); distant metastases: 12 (13%.5%). Among 35 pts with a local relapse, 14 had SLT (cryotherapy:13; cyberknife:1). Reasons to not performed SLT were: advanced age or poor performance status: 10; Gleason 8-10: 2; T3 on MRI: 2; Patient refusal (fear of incontinence): 7. Among 22 pts with a nodal relapse, only 3 could have salvage EBRT. Reasons to not performed SLT were: old age or poor PS: 5; extensive nodal relapse: 8; local and nodal relapse: 6. At the end, 57 pts (64%) are potentially eligible for SLT and 17 (19%) could have it. Conclusions: In routine practice, in a population of 89 pts with a BR, 64% are eligible for SLT but 19% could have it. Main reasons for not having SLT were absence of target lesions, extensive disease, or advanced age. This result justified the realisation of an extensive staging at the time of BR after EBRT or brachytherapy.

BACKGROUND. In patients with lymphoma who had a poor prognosis, pretransplantation 18-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) was important for the evaluation of response and outcome. However, little is known about the correlation of FDG-PET with post-transplantation PET. The current study was designed to ascertain whether positive pretransplantation PET images are modified by the conditioning regimen. METHODS. Sixty consecutive patients who had achieved remission and underwent consolidation by autologous stem cell transplantation (ASCT) had PET images obtained before ASCT (after 3 or 4 chemotherapy cycles) and 100 days after ASCT. The correlation was explored between the presence of abnormal 18-FDG uptake (PET positive) or its absence (PET negative) and patient outcomes. RESULTS. Before ASCT, 31 patients achieved complete remission (CR), and 23 patients achieved uncertain CR. Before ASCT, 44 patients (75%) were had negative PET images; and, after ASCT, 48 patients (80%) had negative PET images. One year after ASCT, the estimated event-free survival (EFS) rate was 80% in patients who had negative pre-ASCT PET images compared with 43% in patients who had positive pre-ASCT PET images (P = .0002). The EFS rate was 81% in patients who had negative post-ASCT PET images compared with 25% in patients who had negative post-ASCT PET images (P < .0001). In multivariate analysis, only the results for pre- and post-ASCT PET images retained prognostic value, with relative risks of failure estimated at 4.9 and 11.9, respectively. CONCLUSIONS. A positive pre-ASCT PET image indicated a high risk of ASCT failure, which was increased by a positive post-ASCT PET image. For patients with lymphoma who have positive pre-ASCT PET images, more investigations using new treatment approaches will be required. For patients who have negative pre-ASCT PET images, obtaining post-ASCT PET images does not seem to be mandatory. Cancer 2007. © 2007 American Cancer Society.

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin's lymphoma with two distinct molecular cell-of-origin (COO) subtypes known as germinal center B-cell (GCB) or activated B-cell (ABC). DLBCL subtypes have been reported to be prognostic and potentially predictive of treatment benefit, underscoring the need for a precise and accurate CDx test (Roschewski, Nat Rev Clin Oncol, 2014). NanoString's LST was developed to enable identification of the COO subtypes on the nCounter® Dx Analysis System using formalin fixed paraffin embedded (FFPE) tissue specimens based on the previously developed Lymph2Cx gene expression profiling assay (Scott, Blood 2014). The test assigns the COO subtypes based on a Linear Predictor Score (LPS) that is calculated using a weighted sum of the gene expression. The LST is currently being used as a CDx in a phase III global clinical validation trial (clinicaltrials.gov NCT02285062) to identify newly diagnosed DLBCL patients of the ABC type who may preferentially respond to lenalidomide. The LST was previously reported to be a highly precise and accurate method of determining DLBCL subtypes (ABC and GCB) when using FFPE excisional/surgical biopsy tissue specimens as a test input (Wallden, JCO 2015). Although excisional biopsies are recommended for DLBCL diagnosis by current ESMO and NCCN guidelines, recent studies have reported excellent sensitivity and specificity in diagnosing malignant lymphomas by core needle biopsy (CNB) leading to increased usage of this method (Hu Q, Am J Clin Pathol, 2013, de Kerviler, Best Pract Res Cl Ha, 2012). The aim of the current study was to assess the analytical performance of the LST when using CNB samples as a test input. Methods: Recently archived CNB and small biopsy DLBCL samples were procured from Oregon Health & Science University (Portland, OR) (n=23), Hôpital Saint-Louis (Paris, France) (n=19), and Asterand Bioscience (n=12). Both nodal and extra-nodal tissue sites were included. Pathology review was performed on an H&E stained slide from each tissue sample to identify the area of DLBCL. Unstained slide mounted FFPE tissue sections (5 µm) were prepared from each sample for assay processing. The RNA extraction and LST procedures were the same as reported previously for surgical biopsy samples (Wallden, JCO 2015). The number of sections used for each RNA extraction was based on the tumor surface area (TSA) measured on the slide (typically 4-6 slides for TSA Results: Of the 54 total samples tested, 51 provided test results (failures were due to RNA degradation). With the 51 passing samples, an assay pass rate of 97% (144/148) was achieved. The total tissue area input into the test was correlated to RNA yield (R2 =0.54). The LPS was highly reproducible across sample replicates (Figure 1) with a total assay standard deviation of 59 LPS units ( Conclusions: In this study we demonstrated robust performance of the LST using FFPE DLBCL CNB/small biopsy samples. Our data support that sufficient RNA yield and gene expression quality can be achieved from biopsy samples with measured TSA of 2 mm2 or greater. We also show that the analytical performance of the LST is comparable between CNB/small biopsy samples and surgical biopsies and that the principal component of gene expression variation is LPS. The LST sample input requirements for the ongoing phase III trial will be updated to include CNB/small biopsy samples to accommodate clinical practice. Disclosures Storhoff: NanoString Technologies, Inc.: Employment, Other: Stock . Wallden:NanoString Technologies, Inc.: Employment, Other: Stock. Braziel:Oregon Health & Sciences University: Employment. Thieblemont:St. Louis Hospital, Paris, France: Employment. Hood:NanoString Technologies, Inc.: Employment, Other: Stock. Ravi:NanoString Technologies, Inc.: Employment, Other: Stock. Dennis:NanoString Technologies, Inc.: Employment, Other: Stock. Dowidar:NanoString Technologies, Inc.: Employment, Other: Stock. Danaher:NanoString Technologies, Inc.: Employment, Other: Stock. Dunlap:Oregon Health & Sciences University: Employment. Briere:St. Louis Hospital, Paris, France: Employment. de Kerviler:St. Louis Hospital, Paris, France: Employment. Ferree:NanoString Technologies, Inc.: Employment, Other: Stock, Patents & Royalties: NanoString Technologies, Inc..

It is commonly admitted that the diagnosis of lymphomas can be assessed by the image-guided needle biopsy (IGNB) of deep lymph nodes. However, when peripheral lymph nodes are present, surgical dissection remains the standard strategy. The aim of this study was to evaluate the diagnostic yield of IGNB of peripheral lymph nodes in patients with suspected lymphomas. The records of 180 multisampling IGNBs of peripheral lymph nodes in 180 patients were reviewed. One hundred and twenty-three IGNBs were observed at first diagnosis and 57 at progression using large-cutting core-biopsy needles ranging between 18 G and 14 G in size. Immunohistochemistry studies were performed in all cases and at least one biopsy was systematically frozen. A diagnosis of lymphoma with sufficient information such that a therapeutic decision could be made was obtained in 146 of the 152 patients with lymphoproliferative disorders (96%). IGNB was equally effective in making the correct diagnosis of lymphoma at the time of original diagnosis than at relapse. The results did not depend on the biopsy site, lymph nodes size, or needle type. We recommend that IGNB may be performed as an initial procedure for the diagnosis of lymphomas either in the presence of peripheral or deep lymph nodes, as it avoids surgery.

Bartonella henselae, previously called Rochalimaea henselae, is the causative agent of cat scratch disease (CSD) in immunocompetent subjects and bacillary angiomatosis in immunocompromised ones. Bone lesions are common in bacillary angiomatosis, but not in CSD. We present the case of a patient with a renal transplant treated by immunosuppressive therapy who developed a sternal abscess with a histological pattern of CSD. The CT pattern was that of a lytic bone lesion with adjacent fluid collection. The diagnosis was made on the basis of a polymerase chain reaction amplification performed on bone material. Bartonella henselae is a newly described bacteria that causes CSD in a normal host and bacillary angiomatosis in immunocompromised patients. We report a case of an osteolytic lesions of the sternum with adjacent fluid collection related to CSD, which occurred in a patient with a renal transplant.

Consolidative autologous stem-cell transplantation (ASCT) is a valuable option in high-risk or disease recurrence large-cell non-Hodgkin lymphoma patients (NHL); however, its long-term toxicity must still be assessed.Among the 439 lymphoma patients transplanted at our institution from January 1, 1993, to January 1, 2002, 158 exhibited aggressive NHL. The median age of the patients was 46 years (range, 18-69), 98 males and 60 females. Ninety (57%) patients received first-line ASCT. The median number of prior chemotherapy regimens was 2 (range, 1-10). Thirty-eight (24%) patients received total body irradiation conditioning. Here we report the adverse events which occurred at least 30 days after ASCT and before disease recurrence.After a median follow-up of 3 years, the overall and disease-free survival rates were 61% and 55%, respectively. Sixty-eight late adverse events affected 43 (27%) patients, leading to a cumulative incidence of 34% at 3 years. Infections were the most frequent adverse events (n = 13), followed by neurologic (n = 12), pulmonary (n = 6), or cardiovascular (n = 4). Eight malignancies were diagnosed (six solid, two hematologic), leading to a cumulative incidence of 3.7% at 3 years. Taking into account the competing risks, multivariate analysis revealed that the number of progressions (relative risk [RR] = 2.68) and a mitoxantrone-containing conditioning regimen (RR = 2.98) significantly increased the incidence of late toxicity.ASCT is effective in patients with aggressive NHL with a poor prognosis. However, careful long-term follow-up of survivors is recommended because of the increase in malignant and nonmalignant toxicities.

Frija G, Clement O, de Kerviler E. Overview of contrast enhancement with iron oxides. Invest Radiol 1994;29:S75–S77.

8560 Background: Spinal cord compression (SCC) in non-Hodgkin lymphoma (NHL) is rare but associated with an increased risk of central nervous system (CNS) relapse. Our objective was to retrospectiv...

e20026 Background: Fine-needle aspiration cytology (FNAC) is used in most of experienced centers to confirm melanoma metastatic spread to the lymph node. In our University Hospital, UltraSound-guid...

Extranodal lesions in Hodgkin disease may develop and spread to virtually any organ system, simulating other neoplastic or infectious diseases. It is important to determine whether extranodal involvement represents a primary manifestation or dissemination of systemic disease, which has a poorer prognosis. Computed tomography (CT) is the preferred modality, although ultrasonography and magnetic resonance (MR) imaging may also be helpful. CT is superior to conventional radiography in assessing chest disease, although MR imaging is more sensitive than CT in detecting chest wall involvement. CT is preferred for evaluating hepatic lymphoma and has proved particularly valuable in diagnosing gastric lymphoma and detecting renal or perirenal masses. CT and MR imaging are equally effective in detecting brain Hodgkin disease; however, the latter is superior in the detection of extracerebral tumor deposits in the subdural or epidural space. MR imaging is also preferred for evaluating meningeal and spinal cord involvement. Both MR imaging and CT allow excellent assessment of bone texture and accurate analysis of tumoral bone invasion, but MR imaging is superior in demonstrating bone marrow infiltration, and CT is superior in delineating the extent of cortical bone destruction. In the future, metabolic positron emission tomography may provide more information about extranodal lymphoma than do the current imaging modalities.

BACKGROUND It is now commonly admitted that the diagnosis of recurrence of lymphoma can be assessed by image-guided needle biopsy (IGNB). However, the means of obtaining tissue for the original diagnosis of lymphoma is often surgery. The aim of this study was to compare the accuracy of IGNB at the time of diagnosis and at the time of recurrence or progression. METHODS The authors performed 212 IGNBs on 194 patients who eventually had a diagnosis of lymphoma. One hundred three IGNBs were obtained at original diagnosis and 109 at recurrence or progression. Large-cutting core-biopsy needles, ranging in size from 20 gauge to 14 gauge, were used. Immunohistochemistry studies were performed in all lymphoma cases. RESULTS A diagnosis of lymphoma with subtyping was obtained in 88% of all cases, in 85% at initial diagnosis, and in 89% at follow-up. Therapy was initiated on the basis of IGNB in 93% of all cases, in 91% at initial diagnosis, and in 94% at follow-up. Benign complications occurred in 7.5% of cases and did not require specific treatment. IGNB was equally effective for making a specific diagnosis of lymphoma and initiating therapy at the time of original diagnosis and at follow-up. CONCLUSIONS The authors recommend that IGNB be performed as the initial procedure for the diagnosis of lymphoma in the absence of peripheral lymph nodes, either at presentation or at recurrence. Cancer 2000;89:647–52. © 2000 American Cancer Society.

Purpose: This study was designed to evaluate the efficacy of extracorporeal lithotripsy (ECL) in the treatment of salivary stones. Patients and Methods: In a prospective study, an additional 15 patients suffering from sialolithiasis were treated by applying extracorporeally generated shock waves. No patients needed general anaesthesia, sedatives, or analgesics. Results: Treatment was effective in 80% of the 15 patients in this series (5 total efficacy and 7 partial efficacy). Only minor complications were observed. Conclusion: Lithotripsy is a promising nonsurgical therapy for the treatment of sialolithiasis.

McArdle's disease is an energy-dependant disorder of skeletal muscle caused by the inability to break down glycogen. The aim of this study was to quantify fatty replacement in patients with McArdle's disease. Calf and thigh axial spin echo T 1 -weighted magnetic resonance (MR) images (repetition time 500 ms, echo time 25 ms) were obtained at 0.5 T in nine patients with McArdle's disease (age 51 ± 16 years, range 26–74) and nine sex- and age-matched healthy subjects (age 52 ± 16 years, range 29–78) to quantify intramuscular fat. Regions of interest were drawn manually, encompassing the largest cross section of muscle. A fatty replacement index (IF) was determined from histograms of signal in the regions of interest in calf and thigh muscles. In normal subjects, IF = 3.6 ± 2.8% in calf and 4.9 ± 2.3% in thigh. In patients, IF = 11 ± 9.3% in calf and 13.5 ± 10.4% in thigh, significantly different from IF values in normal subjects ( p = .03). IF correlated well with age in patients ( p = .03). In older patients, up to 25% of the muscle volume was replaced by fat. Patients with McArdle's disease, usually weakly disabled, exhibit significant muscle fatty replacement on MR images. These findings suggest a progressive muscle loss over time related to the disease process.

In McArdle's disease (myophosphorylase deficiency) exercise intolerance is generally attributed to a lack of glycogenolysis, which decreases energy production during exercise. Magnetic resonance imaging data have recently suggested an impairment of the increase in muscle perfusion during exercise in these patients. We have tested this hypothesis by direct measurement of local muscle perfusion increase. Increase in muscle perfusion was assessed by positron emission tomography with oxygen-15 labelled water in five patients with McArdle's disease and five age- and sex-matched healthy volunteers. Radioactivity was measured in both forearms before and after exercise of the right forearm. The exercise intensity was biochemically assessed by in vivo phosphorus-31 magnetic resonance spectroscopy. The estimated increase in muscle perfusion with exercise was 5.7+/-5.5-fold in the patients (range 1.5-12.8) and 22.3+/-12.0-fold in the healthy subjects (range 10.1-37) (P=0.022). The results show a significant impairment of increase in muscle perfusion with exercise in McArdle's disease. Thus patients may suffer not only from a direct lack of glycogenolysis but also from indirectly impaired vasodilation.

Abstract 2860 Introduction. Histological lymphoma diagnosis of adult patients with bulky mediastinal mass is either HL or PMBL, two distinct diseases with a specific outcome. PET interpretation is often difficult for mediastinal lymphoma because of the volume of the tumor and the presence of blood pool. No specific criteria for interpretation of interim-PET have yet been defined in this clinical entity. The purpose of this study was to investigate the prognostic value of qualitative and semiquantitative evaluations of interim-PET in mediastinal lymphoma. Methods. We retrospectively included 72 patients with either HL (n=48) or PMBL (n=24), previously untreated, aged under 60 at diagnosis and who underwent at least one interim-PET evaluation. Patients with sub-diaphragmatic or medullar localisations of lymphoma were excluded. All PET scans were reviewed. Qualitative evaluation included global visual evaluation (GVE) (positive or negative) and 5 points-scale (5PS). Semiquantitative evaluation consisted in maximum standardized uptake value (SUVmax) and SUVmax reduction between the baseline PET (PET0) and the evaluation performed after two (PET2) or four (PET4) cycles of chemotherapy. Prognostic impact was evaluated on the event-free survival (EFS), defined as disease progression/first relapse (n=18) or death (n=2). ROC (Receiver Operating Characteristic) curve was used to assess the value of SUVmax reduction in discriminating future deaths or relapses, based on area under the curve (AUC). The “best“ cut-off that provides both the lowest false positive and the lowest false negative rates was computed. Results. Median age was 29 (24 - 35), 60% male. Tumoral mass was more than 7.5 cm in 70% of the patients, and M/T ratio>= 0.35 in 79%. Median SUVmax at baseline, PET2 and PET4 were 12.8 (4.1;33.2), 1.9 (1.7;3.1), and 2.4 (1.7;3.1), respectively. With a median follow-up at 24 months, 2-year event-free survival (EFS) was 67%, without significant difference between HL and PMBL (p=0.98). Except for ECOG performance status in PMBL, neither clinical nor biological feature was predictive for EFS. Using GVE, a negative PET2 (n=36/59) and PET4 (n=24/34), were achieved in 61% and 71%, respectively. GVE and 5PS have a significant negative predictive value (NPV) at PET2 (HR=3.2, 95%CI: 1.2–8.2; p=0.012, and HR=1.9, 95%CI: 1.1–3.3, p=0.01) and at PET4 (HR=13.9, 95%CI: 3.5–55; p=0.0001, and 2.6, 95%CI: 1.5–4.7, p=0.001 respectively), with a 2-year estimated EFS of 69% for PET2-negative patients versus 51% for PET2-positive patients (p=0.012), and of 86% for PET4-negative patients versus 20% for PET4-positive patients (p=0.001). An optimal cut-off of 81% SUVmax reduction from PET0 to PET2 or PET4 yielded a 2-year estimated EFS of 70% in patients with reduction of more than 81%, versus 47% in those with reduction of 81% or less (p=0.004). In the HL subgroup, GVE and SUVmax reduction higher than 81% at PET2 (p=0.0001, p=0.015, respectively) and PET4 (p=0.004, p=0.015, respectively) showed significant prognostic values for EFS. In the PMBL subgroup, neither qualitative nor semiquantitative evaluation at PET2 was predictive for EFS. At PET4, GVE and 5PS were strongly predictive for EFS (p=0.005, p=0.0001). Patients with SUVmax reduction higher than 81% between PET0 and PET4 reached a 67% 2-year EFS, while patients with lower SUVmax reduction had only a 33% 2-year EFS (p=0.13). Conclusion. The cut-off value of SUVmax reduction estimated for predicting EFS with best accuracy in mediastinal lymphoma was 81%. Although the SUV semiquantification helps to reduce the number of false positives, visual global analysis had a significant negative predictive value in interim-PET in mediastinal lymphoma, with a possible very early prediction, as early as PET2 in HL, and a better prediction at PET4 than PET2 in PMBL. Disclosures: No relevant conflicts of interest to declare.

Objectifs pedagogiques Montrer l’apport et les limites de l’IRM dans le bilan d’extension des tumeurs. Presenter la place de l’IRM en radiologie interventionnelle oncologique. Montrer les perspectives qu’offrent l’IRM fonctionnelle et l’IRM moleculaire en oncologie. L’IRM occupe desormais une place importante a toutes les etapes de la prise en charge d’un patient en cancerologie : pour le diagnostic, le bilan d’extension, le suivi therapeutique et le traitement. Neanmoins, en aucun cas un examen standard unique permettra d’apprehender ces different aspects. L’indication de chaque examen devra etre discutee pour optimiser la tehnique en prenant en compte les contraintes de temps et la disponibilite de la machine. Le but de cette seance est de montrer le potentiel et les limites de l’IRM a chaque etape de la prise en charge du patient en cancerologie.

Background. Mantle cell lymphoma is one of the most refractory B-cell lymphomas. Despite the recent improvement of novel therapeutic strategies including high dose therapy and the introduction of immunotherapy, MCL patients are not cured by conventional therapeutic strategies. The increasing understanding of the MCL cell biology leads to the development of new drugs targeting to molecular mechanisms of the disease. Among the specific genes found to be overexpressed in MCL by gene expression profiling analysis, farnesyltransferase (FTase) encodes for an enzyme essential in the post- translational modifications of proteins that require prenylation for conversion to mature forms, allowing their participation in various signaling pathways regulating growth and survival. We recently demonstrated that inhibition of FTase by tipifarnib (Zarnestra) is associated in vitro with growth inhibition and apoptosis of MCL cell lines and in vivo with tumor xenograft stability. To determine the efficacy, the safety profile and the toxicity of tipifarnib in MCL, we conducted a phase II trial in patients with refractory MCL, and we evaluated the response considering published molecular predictors. Methods. Primary endpoint was the efficacy measured by the evaluation of the overall response rate (ORR) at 4 cycles, and, in case of response, at 6 cycles. Planned sample size of the study was 27 evaluable patients enrolled for an analysis based on an optimal two-stage design comprising 11 patients for the first stage and 16 for the second stage, under the hypothesis of an ORR of 35% to conclude for an effective drug and an ORR of 10% to conclude for an ineffective drug. Tipifarnib was administered at 300 mg orally twice daily for the first 21 days of each 28-days cycle for 4 to 6 cycles. Prediction of response was retrospectively evaluated in the initial tumor biopsy by the analysis of the 2-gene classifier, the RASGRP1/APTX gene expression ratio, and the AKAP13 expression level. Results. Eleven patients with refractory MCL were included in the analysis. Median number of lines of therapy before tipifarnib was 2.5 (range 1–7). Median age was 71 (range 66–79). All patients presented with stage IV disease and with good performance status. At 4 cycles of tipifarnib, 1 patient presented a complete response and 10 patients were in progressive disease. Two patients progressed during or after the first cycle, three patients after 3 cycles, and five patients after 4 cycles. No grade III-IV hematological toxicities were recorded. One patient presented an unrelated neurological symptom after the first dose administered. Evaluation of the molecular prediction of response to tipifarnib was realized for 3 patients: one responder patient and two non-responder patients. Results showed an increase in the RASGRP1/APTX gene expression ratio and a decrease in AKAP13 expression in the responder patient, and a decrease in the RASGRP1/APTX gene expression ratio and an increase in AKAP13 expression in the non-responder patients. This corresponds to the expected results of the response prediction to tipifarnib. Conclusion. Tipifarnib in refractory MCL was beneficial for only one patient. Response could be exactly predicted by specific molecular predictors of response evaluated in the initial tumor biopsy. These results demonstrate the necessity of categorizing molecularly the patients when targeted therapies are proposed to select those patients that might respond to.

Introduction : Assessment of therapeutic response using 18-Fluoro-deoxy-glucose (FDG) positron emission tomography (PET) is useful to determine prognosis in lymphoma. In poor prognosis lymphoma patients, it may have an important value in the pre-transplant evaluation and help to transplant-decision making. But the impact on patient outcome of post-transplant assessment is unknown. Patients and methods: In our department, between July 2004 and December 2005, 60 consecutive patients (M/F ratio= 37/23) who achieved tumor response and received high-dose chemotherapy plus autologous-stem-cell transplantation (ASCT) were prospectively explored with PET, prior to ASCT (after 3–4 chemotherapy cycles) and 100 days after ASCT. PET images were evaluated without knowledge of conventional imaging and clinical history. Presence (PET positive) or absence (PET negative) of abnormal FDG uptake was related to event-free survival (EFS) and overall survival (OS). Results :50 patients had non-Hodgkin lymphoma (20 diffuse-large-B-cell (DLBCL), 8 mantle-cell, 16 follicular, 4 T-large-cell, 2 Burkitt) and 10 Hodgkin’s lymphoma. Median age was 52 ranging from 19 to 68 years. At diagnosis, 9 patients had 2–4 performance status, 40 elevated LDH, 30 extranodal involvement and 53 staged 3–4. Tumor bulk was above 10 cm in 14 patients. 22 patients received front-line ASCT mainly after ACVBP (n=14) or CHOP. Platinum-based salvage chemotherapy (DHAP, n= 26) was the most frequently used for 27 relapses and 11 refractory diseases. 40 patients received Rituximab with chemotherapy. Prior ASCT, there were 31 complete remission (CR), 23 uncertain CR and 6 partial remission. Conditioning regimen was BEAM in 39 patients; Zevalin BEAM in11, Total Body Irradiation was used in 10. 44 patients (75%) were pre-ASCT-PET negative and 48 (80%) post-ASCT-PET negative. 6 patients (10%) converted from pre-ASCT-PET positive to post-ASCT-PET negative (2 Hodgkin, 1 mantle, 2 follicular, 1 DLBC) and 2 patients (3%) converted from pre-ASCT-PET negative to post-ASCT-PET positive (1 pulmonary infection, 1 early relapse in DLBC). One year after ASCT, 10 patients died (OS 80%) and 17 relapsed (EFS 67%). OS was estimated to 90% in pre-ASCT-PET-negative patients vs. 51 % in PET-positive (p=0.0003), EFS was 75% vs. 43%, respectively (p=0.001). OS was estimated to 87% in post-ASCT-PET-negative patients vs. 48% in PET-positive (p Conclusion: A positive PET after induction chemotherapy indicates a high risk of ASCT failure; in addition, this risk of failure is increased by a positive PET after ASCT. In pre-ASCT-PET-positive patients, more experimental approaches are needed. In pre-ASCT-PET-negative patients, post-ASCT-PET assessment may be omitted.