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Resume L’immunotherapie avec les inhibiteurs de points de controle immunitaire est devenue le traitement de reference dans certains types tumoraux, tels que le melanome et le cancer bronchique non a petites cellules. Contrairement aux therapies conventionnelles (chimiotherapie ou therapies ciblees), l’immunotherapie ne cible pas directement la cellule tumorale et permet de restaurer l’immunite antitumorale. Ce changement de paradigme impacte notamment l’imagerie oncologique et notamment la tomographie par emission de positons au 18fluor-fluorodesoxyglucose couplee a la tomodensitometrie (TEP-TDM au 18F-FDG). En effet, de nouveaux profils de reponse ou de progression ont ete mis en evidence, tels que la pseudo-progression, l’hyperprogression, la reponse dissociee, la reponse prolongee et l’effet abscopal (combinaison radio-immunotherapie). Ces profils « atypiques » ont conduit a une adaptation des criteres d’evaluation therapeutique. De plus, certains biomarqueurs extraits a partir de l’imagerie TEP-TDM au 18F-FDG pourraient permettre d’identifier precocement les candidats a l’immunotherapie, ce qui est actuellement un enjeu clinique majeur. En cours de traitement, la TEP-TDM au 18F-FDG peut egalement aider au diagnostic precoce de certains effets secondaires immuno-induits. D’un point de vue plus fondamental, le decryptage du dialogue entre la tumeur, son microenvironnement et les organes lymphoides (rate et moelle osseuse) est utile pour comprendre les mecanismes physiopathologiques de l’immunoresistance. En imagerie TEP-FDG, il semble exister une correlation entre l’activite metabolique de la moelle osseuse et le profil d’expression de certains genes impliques dans la composition cellulaire du microenvironnement tumoral, directement lie au phenotype immunosuppressif des tumeurs. Enfin, l’imagerie avec immuno-TEP, a partir d’anticorps specifiques ciblant les molecules de points de controle immunitaire, les marqueurs de lymphocytes T ou des biomarqueurs de l’activation immunitaire, permettra vraisemblablement d’offrir une approche theranostique indispensable a l’ere de la medecine de precision.

Primary Central Nervous System Lymphoma (PCNSL) is a rare disease with different therapeutic implications than systemic lymphoma. In this study, we evaluated whole-body 18FDG-PET/CT for pre-chemotherapy imaging of suspected PCNSL. One hundred and thirty consecutive immunocompetent patients were retrospectively included. The results of initial 18FDG-PET/CT, contrast-enhanced CT (CeCT) and bone marrow biopsy (BMB) when available were compared to a gold standard based on pathological diagnosis or follow-up. CNS lesion pathology showed large B-cell lymphoma in 95% of patients, including 11 patients with primary vitro-retinal lymphoma. Ten patients (8%) where ultimately diagnosed with systemic lymphoma involvement, including five pathologically confirmed cases, all of which were detected by 18FDG-PET/CT. 18FDG-PET/CT showed incidental systemic findings unrelated to lymphoma in 14% of patients. An SUVmax threshold of nine enabled good discrimination between systemic lymphoma and other lesions (sensitivity 92% and specificity 89%). CeCT and BMB performed in 108 and 77 patients respectively revealed systemic lesions in only three patients. 18FDG-PET/CT detected concomitant occult systemic involvement in a non-negligible proportion of suspected PCNSL cases (8%). In this setting its sensitivity is higher than that of CeCT. All of our patients ultimately diagnosed with concomitant systemic involvement had positive 18FDG-PET/CT. We believe it constitutes a safe one-stop shop evaluation for the systemic pre-treatment imaging of suspected PCNSL.

It is now well demonstrated that (18F)-fluorodeoxyglucose PET/CT is the most accurate imaging method for determining disease extent in Hodgkin lymphoma. Thus, up-front PET/CT is mandatory for involved node radiation therapy design. For a proper use of this new imaging modality for radiotherapy, some adaptations should be made to the PET/CT acquisition as well as to the report. Initial PET/CT should be performed in the radiotherapy treatment position. Nuclear medicine physicians should report to the radiation oncologist the precise location of each involved lymph node, for which the use of a common atlas of upper diaphragmatic nodal stations could be useful. All these new procedures have to be implemented in close collaboration among the different medical specialists providing care to Hodgkin lymphoma patients. We report here the usual procedures of PET/CT acquisition in the radiotherapy environment and propose a more sophisticated description of the different lymph nodes for a more efficient nuclear medicine report to the radiation oncologist.

Background In contrast to the high cure rates in young patients (pts) treated with anthracycline-based chemotherapy, classical Hodgkin lymphoma (cHL) prognosis is poor in elderly pts, and very few data exist for pts considered too frail to receive standard-dose chemotherapy. In those patients, limited therapeutic options are available. Among the new immune-oncology drugs, Nivolumab, an anti-PD1 antibody, has demonstrated high response rate and very good tolerance, and is now approved in relapse and refractory (R/R) cHL. However, data on its use in the frontline setting are scarce. Material and methods We designed a prospective, open-label, multi-centric phase II study, to assess the efficacy and safety of nivolumab alone, or in combination with vinblastine in naive pts aged 61 years and older, with cHL and coexisting medical conditions. Pts were eligible if they had a Cumulative Illness Rating Scale-Geriatric (CIRS-G) score of 6 or more. Treatment consisted in an induction phase of 6 nivolumab injections, delivered at a flat dose of 240 mg every 14 days. Early assessment was done at 12 weeks by PET-CT and CT-scan. Pts who achieved complete metabolic response (CMR) at early assessment completed treatment with nivolumab monotherapy for 18 additional cycles (consolidation phase). Pts who obtained partial metabolic response (PMR) or non metabolic response (NMR, stable disease) received a combination of 18 cycles of nivolumab plus vinblastine, administered intravenously. The primary objective of the study was to assess the CMR rate based on central review at the end of treatment (EOT). Results From August 30th, 2018 to April 28 th, 2020, 64 pts were included in 31 centers, which composed the full analysis set (FAS), used for safety evaluation. Among these 64 pts, 56 pts were fully evaluable and constituted the efficacy set (ES) used for the efficacy analysis (8 pts progressed early or were not assessed by PET-CT). The median age at inclusion in the ES was 75 years [range: 62-91]. Patients had a median CIRS-G score of 10 [range: 6-18] at baseline, and a median G8 score of 12.5 [range: 6-17]. Seventy-three percent of pts had a stage III-IV disease and 42.9% of pts had B symptoms. At EOT, 16 pts (28.6%) achieved CMR according to central PET-CT review. Ten pts (17.9%) achieved PMR, 10 pts were in NMR (17.9%) and progressive metabolic disease was observed in 17 pts (30.4%). Three pts were not evaluated. The overall response rate at end of induction was 51.9%, (9 CMR and 18 PMR). 23 pts received a consolidation with nivolumab and vinblastine. With a median follow-up of 20.1 months, median PFS was 9.8 months [95% CI: 4.2;12]. 15/64 pts of the FAS died during treatment (23.4%): 6 pts from lymphoma, 2 pts from toxicity of study treatment and 2 pts from concurrent illness. One patient died from toxicity of additional treatment after progression, and 4 pts from other causes. The 2-year overall survival was 76.7% [95% CI: 59.6;87.3]. 49/64 pts (76.6%) experienced at least one AE, among which 32 pts experienced grade 3-4 AEs. The 3 more frequent grade 3-4 AEs were neutropenia (8 pts), sepsis (7 pts) and respiratory tract infection (5 pts). Adverse events were related to nivolumab in 36 pts and led to treatment discontinuation in 19 pts (29.7%). Adverse events of special interest i.e., immune-related AEs, were recorded in 22 pts, including 3 pneumonitis, 1 myocarditis, 1 encephalitis and 1 colitis. Among the 64 pts of the FAS, 34% of pts completed the treatment. The median number of cycles administered was 7 [range: 1-24] for nivolumab and 17 [range: 1-18] for vinblastine. Conclusion The NIVINIHO study is the first study to assess the efficacy and safety of an immune checkpoint inhibitor for first line therapy in elderly, frail patients with cHL. The results suggest that in this setting, a nivolumab-based therapy is active in a subset of pts. Further studies and biological analysis are planned to determine which patients may benefit from this approach. Figure 1 Figure 1. Disclosures Lazarovici: Mundipharma: Other: Travel grant. Bouabdallah: Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Sandoz: Consultancy, Honoraria; Abbvie: Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Morschhauser: Roche: Consultancy, Speakers Bureau; Chugai: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Genmab: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Laribi: Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; BeiGene: Other: Personal Fees; Le Mans Hospital: Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Jansen: Research Funding. Feugier: Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Astrazeneca: Consultancy, Honoraria. Sibon: iQone: Consultancy; Takeda: Consultancy; Abbvie: Consultancy; Roche: Consultancy; Janssen: Consultancy. Ribrag: Gilead: Membership on an entity's Board of Directors or advisory committees; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; GSK: Research Funding; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Nivolumab. Presently labelled for relapse and refractory classical Hodgkin lymphoma and other malignancies

Background: The AHL2011 study demonstrated that a PET-driven strategy allows to deescalate treatment to 4 x ABVD in PET negative patients after 2 cycles of escalated BEACOPP (BEACOPPesc) without loss of tumor control in patients with advanced Hodgkin lymphoma (HL) compared to a non PET-monitored treatment delivering 6 x BEACOPPesc (Casasnovas RO et al, Lancet Oncol 2019). The interim PET results after 2 (PET2) and 4 (PET4) cycles of chemotherapy were found to influence patients PFS and OS independently of IPS. To further refine the patients outcome prediction we evaluate the prognostic value of baseline Total Metabolic Tumor Volume (TMTV) and tumor dissemination (SDmax) in Ann Arbor stage III-IV patients included in the AHL2011 trial. Patients and methods: 634 patients enrolled in the AHL2011 trial with stage Ann Arbor III or IV were included in the study. According to the AHL2011 trial, patients were randomized in a standard arm (6 x BEACOPPesc) or a PET-driven arm (2 x BEACOPPesc and 4 x ABVD in negative PET2 patients or 4 x BEACOPPesc in positive PET2 patients). For each patient, a semi automatic tumor segmentation was retrospectively performed in baseline PET to calculate TMTV using the 41% of SUVmax threshold and compute the maximum distance between the delineated lesions normalized by body surface area (SDmax). Optimal thresholds for TMTV and SDmax were calculated using X-Tile and ROC curve approaches in a randomly assigned training (n=317) and validation sets (n=317). The per protocol PET2 and PET4 responses were analyzed using the modified Deauville criteria (positive if residual uptake >140% background liver). Multivariate analysis included treatment arm, TMTV, SDmax, international prognosis score (IPS), PET2, and PET4 as covariates. The median follow-up was 5.6y. Results : Median TMTV and SDmax were 215 ml and 0.221 m-1 in the whole population and similar in both randomized arms and in the training and validation sets. Optimal cutoffs were 220ml for TMTV (312 patients [49%] had High TMTV) and 0.330 m-1 for SDmax (149 patients [24%] had High SDmax) and similar in the training and validation sets. 5-year PFS for patients with TMTV>220ml was 84.1% vs 90.2% in low TMTV patients (p=0.02) in the whole population (in the training set: 83% vs 89%, p=0.088 ; in the validation set : 86% vs 92% p=0.11). 5-year PFS was significantly lower in patients with SDmax>0.333 m-1 (78.8% vs 89.7%; HR=2.15 [95%CI: 1.38-3.35], p=0.0005) in the whole population (in the training set: 77% vs 89%; p=0.0037); in the validation set: 81% vs 91; p=0.046). The combination of TMTV and SDmax allows to identify two subgroups of patients, those having both low TMTV and low SDmax (n= 281; 44%) and those having high TMTV and/or SDmax (5-year PFS: 92% vs 83.4%; HR=2.24 [95%CI: 1.39-3.62], p=0.0007) (figure 1). In multivariate analysis, high TMTV (p=0.034), high SDmax (p=0.0002), PET2 (p=0.02) and PET4 (p Conclusion: Tumor burden (TMTV) and dissemination (SDmax) assessed on baseline 18FDG PET allow to predict, independently of early reponse to treatment, the outcome of patients with advanced HL. These two parameters overcome the prognosis value of IPS and could be included into new prognostic scores to tailor personalized therapy in advanced Hodgkin Lymphoma. Figure 1 : PFS according to TMTV and SDmax in stage III-IV HL patients enrolled in the AHL2011 study Figure 1 Figure 1. Disclosures Brice: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria; MSD: Honoraria. Ghesquieres: Janssen: Honoraria; Mundipharma: Consultancy, Honoraria; Roche: Consultancy; Celgene: Consultancy, Honoraria; Gilead Science: Consultancy, Honoraria. Stamatoullas-Bastard: Takeda: Consultancy. André: AbbVie: Other: Travel/accomodation/expenses; Roche: Other: Travel/accomodation/expenses, Research Funding; Johnson & Johnson: Research Funding; Incyte: Consultancy; Gilead: Consultancy, Other: Travel/Accommodations/Expenses; Karyopharm: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses; Celgene: Other: Travel/accomodation/expenses; Takeda: Consultancy, Research Funding. Rossi: ROCHE: Honoraria, Research Funding; Takeda: Honoraria; JANSSEN: Honoraria; ABBVIE: Honoraria. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.

Background AHL2011 study (NCT01358747) demonstrated that PET negativity after 2 cycles of upfront BEACOPPescalated (BEA) allows to switch to 4 cycles of ABVD 84% of patients (pts) with advanced Hodgkin lymphoma (HL) leading to reduce immediate treatment toxicity without loss of tumor control (Casasnovas RO, Lancet Oncol 2019). We report an updated follow-up of the study with a focus on the late treatment-related adverse events including secondary primary malignancies (SPM) and unfertility. Methods In AHL2011 823 patients aged 18-60 with a newly diagnosed advanced HL defined by an Ann Arbor stage III, IV or IIB with M/T>0.33 or extranodal involvement were prospectively randomized between a standard arm (n=413) delivering 6 x BEA and a PET-driven arm (n=410) after 2 x BEA delivering 4 x ABVD in PET2- pts and 4 x BEA in PET2+ pts. In both arms PET performed after 4 cycles of chemotherapy had to be negative to complete the planned treatment. We aimed at excluding inferiority of the PET-driven arm of at least 10% compared to the standard arm which was achieved with the analysis on 10/2017. The data cutoff for the present analysis was 29 April 2019. A prospective fertility substudy for patients 24 IU/L twice during 5y follow-up when available, with estradiol < 50pg/ml, and low ovarian reserve (OR) by AMH < 0.16ng/ml. - In males, FSH serum levels and sperm analysis. Results With a 5.6 year median follow-up, 5y PFS and OS were similar in both randomization arms (PFS: 87.5% vs 86.7% ;HR 1.07, 95%CI 0.74-1.57; p=0.67; OS: 97.7% in both arms; HR=1.012, 95%CI 0.50-2.10; p=0.53). In the whole cohort full interim PET assessment predicted patients PFS (5y PFS = 92.3% in PET2-/PET4-, 75.4% [HR= 3.26 ;95%CI 18.3-5.77] in PET2+/PET4- and 46.5% [HR= 12.4 ;95%CI :7.31-19.51] in PET4+ pts respectively; p 5g (HR=0.36, 95%CI 0.14-0.96; p=0.04) but not to arms. In males, median baseline FSH levels were similar in both arms but 19 and 23% experienced severe oligospermia at baseline in standard (n=214) and PET-driven arms (n=210), respectively. Chemotherapy dramatically reduced sperm numeration in both arms but recovery occured more frequently in the PET-driven arm (severe oligospermia at 4-5 year: 50% vs 93%). A total of 84 patients (14.7%) reported pregnancies including 49 (17.2%) in the PET driven arm vs 35 (12.3%) in the standard arm (p=0.12) and required assisted reproductive technology treatment more frequently in the standard arm (23% vs 14%). Conclusions The prolonged follow-up confirms that the PET-driven strategy delivering 4 cycles of ABVD in PET negative patients after 2 cycles of BEA is non inferior compared to standard 6 cycles of BEA. PET4 provides additionnal prognostic information to PET2 and identifies patients with particularly poor prognosis. The PET-driven treatment allows to reduce significantly the risk of infertility in both men (recovery of oligospermia) and women (decreasing by 5 the risk of POI) and improves the chances of spontaneous pregnancy after completion of HL treatment. With the current follow-up the risk of SPM was low (2.7%) and similar in both arms. Disclosures Casasnovas: Roche: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria; BMS: Consultancy, Honoraria; AMGEN: Consultancy, Honoraria; abbvie: Consultancy, Honoraria. Brice:Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; BMS: Honoraria; MSD: Honoraria; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Ghesquieres:Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; CELGENE: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen: Honoraria. Stamatoulas Bastard:Takeda: Consultancy; Celgene: Honoraria; Pfizer: Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Dupuis:Henri Mondor University Hospital Creteil France: Current Employment. Gac:Roche: Consultancy; Takeda: Consultancy. Bouabdallah:Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria. Morschhauser:Genentech, Inc. Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. André:Johnson & Johnson: Research Funding; Celgene: Other, Research Funding; Takeda: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Seattle Genetics: Consultancy; Novartis: Consultancy, Research Funding; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Abbvie: Consultancy; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding. Meignan:ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Demeestere:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; THERAMEX FERRING: Other: TRAVEL, ACCOMMODATIONS, EXPENSES., info:eu-repo/semantics/published

International audience; Background: Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring.Methods: AHL2011 is a randomised, non-inferiority, phase 3 study done in 90 centres across Belgium and France. Eligible patients were aged 16-60 years and had newly diagnosed Hodgkin lymphoma, excluding nodular lymphocyte predominant subtype, an Eastern Cooperative Oncology Group performance status score less than 3, a life expectancy of at least 3 months, an Ann Arbor disease stage III, IV, or IIB with mediastinum-to-thorax ratio of 0·33 or greater than or extranodal localisation, and had received no previous treatment for Hodgkin lymphoma. Randomisation was unmasked and done centrally by the permuted block method. Patients were randomly assigned to standard treatment (BEACOPPescalated given every 21 days for six cycles) or PET-driven treatment. All patients received two cycles of upfront BEACOPPescalated, after which PET assessment was done (PET2). In the standard treatment group, PET2 patients completed two additional cycles of BEACOPPescalated induction therapy irrespective of PET2 findings. In the PET-driven treatment group, patients with positive PET2 scans received the further two cycles of BEACOPPescalated and those with a negative PET2 scan switched to two cycles of ABVD for the remaining induction therapy. In both treatment groups, PET at the end of induction therapy was used to decide whether to continue with consolidation therapy in those with negative scans or start salvage therapy in patients with positive scans (either two cycles of ABVD in PET2-negative patients in the PET-driven arm or two cycles of BEACOPPescalated). BEACOPPescalated consisted of bleomycin 10 mg/m2 and vincristine 1·4 mg/m2 intravenously on day 8, etoposide 200 mg/m2 intravenously on days 1-3, doxorubicin 35 mg/m2 and cyclophosphamide 1250 mg/m2 intravenously on day 1, 100 mg/m2 oral procarbazine on days 1-7, and 40 mg/m2 oral prednisone on days 1-14. ABVD was given every 28 days (doxorubicin 25 mg/m2, bleomycin 10 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 intravenously on days 1 and 15). The primary endpoint was investigator-assessed progression-free survival. Non-inferiority analyses were done by intention to treat and per protocol. The study had a non-inferiority margin of 10%, to show non-inferiority of PET-guided treatment versus standard care with 80% power and an alpha of 2·5% (one-sided). This study is registered with ClinicalTrials.gov, number NCT01358747.Findings: From May 19, 2011, to April 29, 2014, 823 patients were enrolled-413 in the standard care group and 410 in the PET-driven group. 346 (84%) of 410 patients in the PET-driven treatment group were assigned to receive ABVD and 51 (12%) to continue receiving BEACOPPescalated after PET2. With a median follow-up of 50·4 months (IQR 42·9-59·3), 5-year progression-free survival by intention to treat was 86·2%, 95% CI 81·6-89·8 in the standard treatment group versus 85·7%, 81·4-89·1 in the PET-driven treatment group (hazard ratio [HR] 1·084, 95% CI 0·737-1·596; p=0·65) and per protocol the values were 86·7%, 95% CI 81·9-90·3 and 85·4%, 80·7-89·0, respectively (HR 1·144, 0·758-1·726; p=0·74). The most common grade 3-4 adverse events were leucopenia (381 [92%] in the standard treatment group and 387 [95%] in the PET-driven treatment group), neutropenia (359 [87%] and 366 [90%]), anaemia (286 [69%] vs 114 [28%]), thrombocytopenia (271 [66%] and 163 [40%]), febrile neutropenia (145 [35%] and 93 [23%]), infections (88 [22%] and 47 [11%]), and gastrointestinal disorders (49 [11%] and 48 [11%]). Serious adverse events related to treatment were reported in 192 (47%) patients in the standard treatment group and 114 (28%) in the PET-driven treatment group, including infections (84 [20%] of 412 vs 50 [12%] of 407) and febrile neutropenia (21 [5%] vs 23 [6%]). Six (1%) patients in the standard care group died from treatment-related causes (two from septic shock, two from pneumopathy, one from heart failure, and one from acute myeloblastic leukaemia), as did two (

Objectifs Le lymphome cerebral primitif (LCP) est une tumeur cerebrale rare correspondant a une proliferation lymphocytaire maligne limitee au systeme nerveux central. Le diagnostic est suspecte sur l’IRM cerebrale. Il est confirme par examen anatomopathologique et en l’absence d’atteinte lymphomateuse systemique associee. Celle-ci est recherchee a l’aide d’un bilan d’extension comprenant une TDM thoraco-abdomino-pelvienne, une biopsie osteo-medullaire et un examen testiculaire. L’objectif principal de cette etude etait d’evaluer l’interet de la TEP au 18F-fluoro-deoxyglucose (TEP-FDG) dans le bilan d’extension initial des suspicions de LCP. Les objectifs secondaires etaient d’etudier les performances de la TEP-FDG pour la detection des lesions cerebrales et son eventuel interet pronostique. Materiels et methodes Les examens de 21 patients non immunodeprimes atteints d’un lymphome cerebral et ayant beneficie d’une TEP-FDG avant toute chimiotherapie ont ete etudies. Tous les bilans d’extension systemiques conventionnels etaient negatifs. Les acquisitions ont ete realisees avec une camera TEP/TDM Gemini (Philips). Les patients etaient a jeun depuis 6 heures avant l’examen et etaient mis au repos neurosensoriel dans une piece sombre et sans bruit apres l’injection de 5 MBq/kg de 18FDG. La fixation etait evaluee visuellement et par le calcul de la SUVmax (regions d’interet volumiques placees sur la lesion la plus hypermetabolique ou a l’aide de l’IRM en l’absence d’anomalie TEP), ainsi que de son rapport a la fixation de l’hemisphere controlateral, du cervelet et du foie. Resultats Chez 3 patients (14 %), une atteinte systemique a ete detectee en TEP-FDG. Celle-ci a pu etre confirmee histologiquement dans un cas et reposait sur un faisceau d’arguments dans deux autres. Le metabolisme des lesions cerebrales etait eleve avec un SUVmax moyen de 15,5. Soixante-dix-huit pour cent (35/45) des prises de contraste visibles en IRM T1 apres injection de Gadolinium se traduisaient par un hypermetabolisme cerebral pathologique. Les prises de contraste infracentimetriques n’etaient visibles que dans 50 % des cas (8/16). Le suivi moyen etait de 17 mois. La survie sans progression a un an etait plus faible dans le groupe de patients ayant les lesions les plus hypermetaboliques (SUVmax tumoral ≥ 15 ; p = 0,015 et rapport SUVmax tumoral/SUVmoyen hepatique > 7). Conclusions Les resultats de ce travail suggerent que la TEP/TDM au 18FDG pourrait avoir un interet dans le bilan d’extension initial des LCP, mais ces resultats necessitent d’etre confirmes de maniere prospective et sur un plus grand nombre de sujets.

Introduction: About 10-15% of patients with localized and 25-30% with disseminated classical HL failed to respond or relapse after primary conventional treatment. For the youngest, autologous stem cell transplantation (ASCT) is a standard of care after salvage chemotherapy leading to an increased disease free survival (DFS). With this strategy 50 to 70% of patients with chemo sensitive disease become eligible for ASCT. As the disease status before ASCT appears to be the most important factor predicting outcome, second line chemotherapy has to be more efficient. Brentuximab-Vedotin (BV) has shown significant activity (SG035-0003) in patients with relapsed or refractory HL. Therefore, it seems logical to use BV in patients treated with ICE before ASCT in order to induce a better Complete Metabolic Response (CMR) rate evaluated by FDG-PET (Deauville score 1-3). Methods: BV was added to ICE in a phase I/II trial chemotherapy trial sponsored by LYSARC with a financial support by Millenium. The optimal dose of BV (1.8 mg/kg) with ICE (3 cycles) was established in the phase I of the study (10 patients). In the second part of the study (phase II), efficacy and toxicity of the Recommended Phase II Dose (RP2D) was assessed. Patients received 2 cycles of BV ICE before evaluation and only CMR received the third course, than an injection of brentuximab alone before ASCT. Primary endpoint was CMR after 2 cycles of treatment. Results: Final analysis was performed in 42 patients for toxicity and 39 patients for the efficacy set. Baseline characteristics were median age: 30 years (range: 18-65), Sex ratio (M/F): 27/15, nodular sclerosis histology in 83%, stage III/IV in 67 % and status of the disease: 12 refractory patients and 30 relapsed patients with a median time to first relapse of 19 months (9-159). First-line treatment was escBEACOPP (n =21) ABVD (n= 17) OEPA/copdac (n= 2) PVAB (n=1) CHOP (n =1). All patients received the two first cycles, 78.6 % the third cycle and 71 % the brentuximab alone without modification of doses but with delay of at least one cycle in 45 %. Grade 3-4 adverse events were encountered in 35 patients (83%) mainly due to hematologic toxicity (71%) followed by infection (21%) and gastro-intestinal disorders (10%). No neuropathy and no toxic death were observed. Most patients (69.2%, n=27) had CMR, followed by PMR (25.6%, n=10). Among the 39 patients, three patients (7.7%) had progressive disease during treatment phase. Leukaphereses were performed in 31 patients (79%) median collected D34+ cells was 7.2 (106/kg) and 20 patients out of the 25 with CMR underwent ASCT. Thirteen patients relapsed mainly during follow-up (10) and no death was observed without progression. The median PFS was not reach and the one-year-PFS was 69% [95% CI: 53%-81%]. Conclusion: Two cycles of BV in R/R HL patients who are treated by ICE chemotherapy allows a CMR in 69.2 % of evaluable patients with sufficient harvest for an ASCT. These results are comparable to other salvage chemotherapies only after two cycles with acceptable toxicities. Disclosures Stamatoullas: Takeda: Consultancy; Celgene: Honoraria. Quittet:Novartis: Honoraria, Speakers Bureau. Morschhauser:F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees. Ribrag:Epizyme: Consultancy, Research Funding; ArgenX: Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses ; MSD: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; AZ: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel, accommodations, and expenses . Brice:Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria.

IF 1.128; International audience; Fluorodeoxyglucose (FDG) positons emission tomography (PET)-computed tomography (CT) is used in many ways at baseline and during the treatment of patients with Hodgkin lymphoma. Many properties of the technique are used in the different steps of patient's management. Initial staging with PET-CT is more accurate than conventional imaging and PET-CT also became the gold standard imaging at the end of treatment with a negative PET-CT mandatory for reaching a complete remission. Early assessment of response by PET-CT is one of the most powerful prognostic factors for progression-free survival of patients with localized and advanced stages and allows guiding treatment. Conversely, previous studies showed that there is no role of FDG PET-CT for the patient's follow-up.; La tomographie par émission de positrons (TEP)-tomodensitométrie au fluorodésoxyglucose est utilisée de différentes manières au moment du diagnostic et pendant le traitement des lymphomes de Hodgkin. Plusieurs particularités de la TEP sont utilisées à différentes étapes de la prise en charge des patients. Lors du bilan initial, la TEP-tomodensitométrie est plus performante que les techniques d’imageries conventionnelles, mais l’est aussi en fin de traitement, un examen normal étant indispensable pour affirmer l’obtention d’une rémission complète. L’évaluation précoce en cours de traitement est un des facteurs pronostiques les plus puissants pour la survie sans progression et pour guider le traitement dans les maladies localisées et disséminées. À l’inverse, la TEP-tomodensitométrie n’a pas de rôle dans le suivi des patients.

The response evaluation criteria in patients with Hodgkin lymphoma (HL) were designed for the assessment of chemotherapy and targeted molecular agents. We investigated the accuracy of 3-mo 18F-FDG PET/CT for the identification of HL patients responding to immune-checkpoint blockade by anti-programmed death 1 antibodies (anti-PD1). We also reported the frequency of new immune patterns of response and progression. Methods: Retrospectively, we recruited consecutive HL patients treated by anti-PD1 (pembrolizumab or nivolumab) at Gustave Roussy from 2013 to 2015. 18F-FDG PET/CT and contrast-enhanced CT scans were acquired every 3 mo. We recorded the best overall response according to the International Harmonization Project Cheson 2014 criteria and LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) (2016 revised criteria). Patients achieving an objective response at any time during the anti-PD1 treatment were classified as responders. Results: Sixteen relapsed or refractory classic HL patients were included. The median age was 39 y (age range, 19-69 y). The median previous lines of therapy was 6 (range, 3-13). The mean follow-up was 22.6 mo. Nine of 16 patients (56%) achieved an objective response. Two deaths occurred due to progressive disease at 7 mo. 18F-FDG PET/CT detected all responders at 3 mo and reclassified best overall response in 5 patients compared with CT alone. A decrease in tumor metabolism and volume (SUVmean, metabolic tumor volume) and increase in healthy splenic metabolism at 3 mo were observed in responders (area under the curve > 0.85, P < 0.04). Five of 16 patients (31%) displayed new imaging patterns related to anti-PD1; we observed 2 transient progressions consistent with indeterminate response according to the LYRIC (2016) (IR2b at 14 mo and IR3 at 18 mo) and 3 patients with new lesions associated with immune-related adverse events. Conclusion: Three-month 18F-FDG PET/CT scans detected HL patients responding to anti-PD1. New patterns were encountered in 31% of patients, emphasizing the need for further evaluation in larger series and close collaboration between imaging and oncology specialists on a per-patient basis.

Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in previously untreated—according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U)—stage I and II HL. The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) and INRT (superiority design). Primary end point was progression-free survival (PFS). Results Of 1,950 randomly assigned patients, 1,925 received an ePET—361 patients (18.8%) were positive. In ePET-positive patients, 5-year PFS improved from 77.4% for standard ABVD + INRT to 90.6% for intensification to BEACOPPesc + INRT (hazard ratio [HR], 0.42; 95% CI, 0.23 to 0.74; P = .002). In ePET-negative patients, 5-year PFS rates in the F group were 99.0% versus 87.1% (HR, 15.8; 95% CI, 3.8 to 66.1) in favor of ABVD + INRT; the U group, 92.1% versus 89.6% (HR, 1.45; 95% CI, 0.8 to 2.5) in favor of ABVD + INRT. For both F and U groups, noninferiority of ABVD only compared with combined modality treatment could not be demonstrated. Conclusion In stage I and II HL, PET response after two cycles of ABVD allows for early treatment adaptation. When ePET is positive after two cycles of ABVD, switching to BEACOPPesc + INRT significantly improved 5-year PFS. In ePET-negative patients, noninferiority of ABVD only could not be demonstrated: risk of relapse is increased when INRT is omitted, especially in patients in the F group.

Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer with a poor prognosis. Locoregional staging is based on dynamic contrast-enhanced (DCE) CT or MRI. The aim of this study was to compare the performances of FDG PET/CT and DCE CT in locoregional staging of IBC and to assess their respective prognostic values. The study group comprised 50 women (median age: 51 ± 11 years) followed in our institution for IBC who underwent FDG PET/CT and DCE CT scans (median interval 5 ± 9 days). CT enhancement parameters were net maximal enhancement, net early enhancement and perfusion. The PET/CT scans showed intense FDG uptake in all primary tumours. Concordance rate between PET/CT and DCE CT for breast tumour localization was 92 %. No significant correlation was found between SUVmax and CT enhancement parameters in primary tumours (p > 0.6). PET/CT and DCE CT results were poorly correlated for skin infiltration (kappa = 0.19). Ipsilateral foci of increased axillary FDG uptake were found in 47 patients (median SUV: 7.9 ± 5.4), whereas enlarged axillary lymph nodes were observed on DCE CT in 43 patients. Results for axillary node involvement were fairly well correlated (kappa = 0.55). Nineteen patients (38 %) were found to be metastatic on PET/CT scan with a significant shorter progression-free survival than patients without distant lesions (p = 0.01). In the primary tumour, no statistically significant difference was observed between high and moderate tumour FDG uptake on survival, using an SUVmax cut-off of 5 (p = 0.7 and 0.9), or between high and low tumour enhancement on DCE CT (p > 0.8). FDG PET/CT imaging provided additional information concerning locoregional involvement to that provided by DCE CT on and allowed detection of distant metastases in the same whole-body procedure. Tumour FDG uptake or CT enhancement parameters were not correlated and were not found to have any prognostic value.

Objectifs Les parametres quantitatifs mesures sur la TEP/TDM au FDG pre-therapeutique sont des facteurs pronostiques precoces superieurs aux indices cliniques dans differents types de lymphomes de stade avance. L’objectif de cette etude etait d’analyser leur interet chez des patients atteints d’un lymphome de Hodgkin (LH) de stade localise inclus dans le bras standard du protocole europeen H10 par des centres LYSA (Lymphoma Study Association). Materiels et methodes Criteres d’inclusion : patients du bras standard de l’essai H10 (traitement par 4 cures d’ABVD suivies par radiotherapie), groupe defavorable (au moins un des criteres : âge > 50 ans, ≥ 4 aires ganglionnaires atteintes, rapport mediastino-thoracique (M/T) ≥ 0,35, vitesse de sedimentation VS≥ 50 ou VS≥ 30 avec symptomes B) ; TEP/TDM initiale avec donnees disponibles pour le calcul du SUVmax. Le volume metabolique tumoral total (TMTV) calcule avec un seuil fixe a 41 % du SUVmax des lesions ganglionnaires, l’indice de glycolyse totale (TLG) et le SUVmax ont ete mesures. Les courbes de survie sans progression (SSP) et de survie globale (SG) ont ete calculees par methode de Kaplan Meier, en fonction du TMTV ou du TLG, avec les seuils obtenus par analyse ROC. Resultats Cent cinquante et un patients (âge median : 31 ans) ont ete inclus : 32 % avaient une VS ≥ 30 avec symptomes B, 50 % une VS ≥ 50 sans symptomes B, 37 % un rapport M/T ≥ 0,35. Le SUVmax, le TMTV et le TLG medians (extremes) etaient de 10,9 (1,6–26,6), 86 cm 3 (3–678) et 419 (8–2775). La SSP et la SG a 5 ans etaient de 83 % et 92 %. Le parametre le plus significatif pour predire la SSP et la SG etait le TLG ( p = 0,0001 HR = 5,6 ; p = 0,005, HR = 6,7). Les patients avec un TLG eleve (> 480) avaient une SSP et une SG a 5 ans de 72 % et 83 % contre 93 % et 98 % pour les patients avec un TLG inferieur. Le TMTV, avec un seuil de 145 cm 3 , etait aussi tres predictif de la SSP ( p = 0,0001 HR = 4,3) et de la SG ( p = 0,033, HR = 4,7). Un SUVmax eleve (> 14) etait associe a une SSP plus courte mais de facon moins significative ( p = 0,03) et sans impact sur la SG ( p = 0,4). Le rapport M/T, la VS> 50 ou l’atteinte d’au moins 4 aires ganglionnaires n’etaient pas predictifs de la SSP. Conclusions Le TLG et le TMTV mesures sur la TEP/TDM pre-therapeutique dans le LH de stade localise sont predictifs de la SG et de la SPP et pourraient permettre de detecter les patients a risque lors du diagnostic.

Hybrid systems associating the sharpness of anatomic images coming from computed tomography (CT) and radionuclide functional imaging (SPET or PET) are opening a new era in oncology. This multimodal imaging method is now routinely used for the diagnosis, extent, follow up, treatment response and detection of occult disease in different types of malignancies with a significant impact on the treatment strategy leading for a change for more than 68% of all investigated patients.

BACKGROUND: Breast cancer recurrence is often suspected on tumor marker rising in asymptomatic patients. The value of fluorine-18 fluorodeoxyglucose (18FDG)–positron emission tomography/computed tomography (PET/CT) imaging to detect recurrence and its subsequent impact on patient management were retrospectively assessed. METHODS: PET/CT scans were performed on 228 asymptomatic patients (mean, 60.8 years; range, 30-91 years) presenting with rising CA 15-3 and/or CEA serum levels. RESULTS: PET/CT scans were positive in 181 patients (79.5%) and normal in 47 patients, whereas 187 true recurrences were diagnosed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT imaging for detection of breast cancer recurrence were 93.6%, 85.4%, 96.7%, 74.5%, and 92.1%, respectively. When compared with the standard workup available in 67 patients, PET/CT imaging had a higher sensitivity and accuracy (94.5% vs 33% and 94% vs 48%, respectively). Recurrences were confirmed by pathology, conventional imaging techniques, or radiological and clinical follow-up beyond 1 year (mean, 34 months; range, 12-67 years) in 32, 130, and 25 patients, respectively. The diagnosis of recurrence led to a treatment modification in 123 patients (54%). CONCLUSIONS: 18FDG-PET/CT imaging is an efficient technique to detect breast cancer recurrence suspected on tumor marker rising in asymptomatic patients. It may thus contribute to improve patient management, providing an earlier diagnosis with complete whole-body staging as a “one-stop shop” procedure. Cancer 2011. © 2010 American Cancer Society.

Resume Cette observation montre l’interet de la TEP/TDM au FDG dans la caracterisation de tumeurs mammaires bilaterales chez une femme jeune sans facteur de risque carcinologique.

7503Background: Escalated BEACOPP (BEA) improves PFS but not OS in pts with advanced HL compared to ABVD and is associated to a higher risk of hematological toxicity, secondary leukemia and inferti...

Purpose: Metaiodobenzylguanidine (MIBG), specifically taken up in cells of sympathetic origin, provides a highly sensitive and specific indicator for the detection of metastases in neuroblastoma. The aim of this study was to correlate early response to therapy by MIBG scan, using a semiquantitative scoring method, with the end induction response and event-free survival (EFS) rate in stage IV neuroblastoma. Patients and Methods: Seventy-five children older than 1 year and with stage IV neuroblastoma had 123I-MIBG scans at diagnosis, after two and four cycles of induction therapy, and before autologous stem-cell transplantation. The scans were read by two independent observers (concordance > 95%) using a semiquantitative method. Absolute and relative (score divided by initial score) MIBG scores were then correlated with overall pretransplantation response, bone marrow response, and EFS. Results: The pretransplantation response rate was 81%, and the 3-year EFS rate was 32%, similar to a concomitant group of 375 stage IV patients. The median relative MIBG scores after two, four, and six cycles were 0.5, 0.24, and 0.12, respectively. The probability of having a complete response or very good partial response before transplantation was significantly higher if the relative score after two cycles was ≤ 0.5, or, if after four cycles, the relative score was ≤ 0.24. Patients with a relative score of ≤ 0.5 after two cycles or a score of ≤ 0.24 after four cycles had an improved EFS rate (P = .053 and .045, respectively). Conclusion: Semiquantitative MIBG score early in therapy provides valuable prognostic information for overall response and EFS, which may be useful in tailoring treatment.

Background: Neaodjuvant endocrine therapy (NET) has demonstrated efficacy in terms of clinical response and outcome in hormone-receptor positive (HR+) post-menopausal patients (pts) with breast cancer (BC) not eligible for primary breast conservative surgery (BCS). However, the monitoring of tumor response to NET is challenging and clinical response is the current gold standard. The aim of the present study was to investigate the contribution of the early metabolic response (eMR) at one month in FDG-PET/CT in a NET setting for post-menopausal pts with HR+, HER2- BC compared to morphological and pathological responses. We also aimed to evaluate the prognostic value of eMR. Methods: This was a prospective and ancillary study of CARMINA 02, UCBG0609 (Cancer in press), a phase II clinical trial evaluating the efficacy of 4 to 6 months neoadjuvant anastrozole or fulvestrant. FDG-PET/CT exams were performed at baseline (M0), after 1 month of treatment (M1: eMR) and pre-Op (late metabolic response: lMR) in 11 pts (74.2 years ± 3.6) from 2007 to 2010. Pts were classified “metabolic responders” (mR) if SUVmax values decrease was ≥ 40% at M1 and “non-metabolic responders” (mNR) if otherwise; lMR was also assessed in mR and mNR groups defined at M1. We compared eMR to morphological response (clinical, breast US and MRI) at M1 and pre-op, to the pathological response according to Sataloff classification and to Ki67 score variation during treatment. Early metabolic response was also correlated with the PEPI (Preoperative Endocrine Prognostic Index) score and survival (overall survival, OS and relapse free survival, RFS). Results: Main results are summarized in Table I. There was a significant difference between mR and mNR pts at M1 (eMR) and pre-op (lMR). One patient with a complete metabolic response at pre-op had the best pathological response (Sataloff TB). Also, mR pts had a better clinical response: 2 partial response (PR) in mR vs 1 in mNR group and 2 mNR patients were classified PD (progressive disease). There was a trend toward better survival for mR pts in OS and RFS (Kaplan-Meier p=0.18 and 0.06, respectively) and all the pejorative events occurred in the mNR group: 3 deaths and 3 metastatic progressions. Besides, no difference in eMR was observed regarding the histological subtype (ductal or lobular; p>0.05) nor the treatment group (p>0.05). Table I: Metabolic, morphological and pathological response at M1, Pre-Op and on the surgical specimen. MR : 5ptsmNR : 6ptsP valueM1SUVmax2.6±1.13.9±1.40.00017 Clinical size42.5mm±11.951.7mm±7.50.19 US size22.6mm±6.334.2mm±2.40.02 MRI size21.2mm±4.239.7mm±4.79.16 E-5 Ki 673.6%±1.98.2%±80.19Pre-OpSUVmax2±1.33.3±1.40.018 Clinical size31mm±12.448.3mm±10.80.035 US size18.5mm±7.331.3mm±9.50.07 MRI size17.9mm±7.134.8mm±7.70.003Surgical SpecimenSataloff (TA+TB vs TC+TD)20% vs 80%0 vs 100%1 PEPI score (I+II vs III)80% vs 20%33 vs 67%0.048 Ki 678.6%±9.812.3%±7.90.41 Conclusions: These preliminary results showed the value of the early metabolic response in FDG- PET/CT in a NET setting compared to the morphological or the pathological responses alone. Early metabolic responders patients had better OS, RFS and PEPI scores. Citation Format: Boughdad S, Champion L, Becette V, Cherel P, Fourme E, Edeline V, Lemonnier J, Lerebours F, Alberini JL. Predictive value of FDG-PET/CT after neoadjuvant endocrine treatment in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-01-03.

Although progression free survival and overall survival of patients with Hodgkin lymphoma (HL) has improved with modern treatment in the past 10 years, 10 % of patients will fail to conventional therapy and die of their lymphoma. The search of new prognostic factors for identifying these high risk patients at diagnosis of HL remains challenging in daily practice. The evaluation of the tumor microenvironnement was shown to help identifying a subset of patients treated with ABVD having a high risk of treatment failure (Tan KL et al, Blood 2012). PET positivity after 2 cycles of chemotherapy allows also identifying a subset of patients with poor outcome (Gallamini, JCO 2007) and PET-guided strategy were developed to improve the management of HL patients in order to either intensify treatment for high risk patients or deescalate treatment for sparing the others from toxicities. The aim of this study was therefore to evaluate the impact of baseline tumor microenvironnement in a large cohort of HL patients prospectively treated with upfront escalated BEACOPP in a randomized phase III clinical trial evaluating a PET-driven strategy (AHL 2011, NCT01358747) and to compare its prognostic value with other clinicopathological markers. Material and Methods Tumoral material was collected from May 2011 to May 2014 from HL patients prospectively enrolled in the AHL 2011 study. The AHL 2011 trial was designed to evaluate in 16-60 years old HL patients with Ann Arbor stage III, IV or high risk IIB, a de-escalade PET-driven strategy after 2 cycles of BEACOPPesc randomly compared to a standard treatment not driven by PET and delivering 6 cycles of BEACOPPesc. PET were centrally reviewed and interpreted according to Deauville criteria. As recently reported (Casasnovas, ASH 2015 Abs 577), the 2y-PFS was similar in the PET-driven (88%) and the standard arm (91%; p =0.79). The tumor microenvironnement was analyzed on formalin fixed paraffin embedded lymph node biopsy obtained for the diagnosis before treatment by morphological evaluation on standard staining (% polynuclear eosinophils, % lymphocytes, % plasmocytes, % histiocytes), and immunohistochemistry (IHC) scoring (score 0-1-2-3) for CD20, CD3, CD68-TAMs (tumor-associated macrophages) and CD163 and were centrally reviewed. Percentage of tumoral cells and EBV status were also analysed. In this analysis, the prognosis value of tissue markers expressions were compared to those of clinical and biological patient's characteristics, and PET results after 2 cycles of escalated BEACOPP. Results Six hundred fifty eight patients with available IHC data out of 823 enrolled in AHL2011 study were included in the analysis. With a median follow-up of 16.1 months, 2-year PFS was 89.4% (95% CI [86.2% ; 91.9%]) and 2-year OS 98.7% (95% CI [96.4% ; 99.5%]). In univariate analysis male gender, at least one extra-nodal involvement, B symptoms, Hemoglobin Among baseline patients characteristics, male gender, hemoglobin In conclusion, CD68 expression was confirmed to be an important prognostic marker in this large prospective cohort of patients treated with upfront escalated BEACOPP in a modern PET-guided strategy. Baseline high CD68 expression is associated to a higher risk of PET2 positivity and the combination of this microenvironment marker and PET2 results allowed identifying a population of patients with high risk of treatment failure. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Brice: Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Bristol Myers-Squibb: Honoraria; Seattle Genetics: Research Funding; Gilead: Honoraria; Roche: Honoraria. Casasnovas:BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; ROCHE: Consultancy, Honoraria, Research Funding.

Purpose This study examines the role of 18 F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) in the implementation of involved-node radiation therapy (INRT) in patients treated for clinical stages (CS) I/II supradiaphragmatic Hodgkin lymphoma (HL). Methods and Material Patients with untreated CS I/II HL enrolled in the randomized EORTC/LYSA/FIL Intergroup H10 trial and participating in a real-time prospective quality assurance program were prospectively included in this study. Data were electronically obtained from 18 French cancer centers. All patients underwent APET-computed tomography (PET-CT) and a post-chemotherapy planning CT scanning. The pre-chemotherapy gross tumor volume (GTV) and the postchemotherapy clinical target volume (CTV) were first delineated on CT only by the radiation oncologist. The planning PET was then co-registered, and the delineated volumes were jointly analyzed by the radiation oncologist and the nuclear medicine physician. Lymph nodes undetected on CT but FDG-avid were recorded, and the previously determined GTV and CTV were modified according to FDG-PET results. Results From March 2007 to February 2010, 135 patients were included in the study. PET-CT identified at least 1 additional FDG-avid lymph node in 95 of 135 patients (70.4%; 95% confidence interval [CI]: 61.9%-77.9%) and 1 additional lymph node area in 55 of 135 patients (40.7%; 95% CI: 32.4%-49.5%). The mean increases in the GTV and CTV were 8.8% and 7.1%, respectively. The systematic addition of PET to CT led to a CTV increase in 60% of the patients. Conclusions Pre-chemotherapy FDG-PET leads to significantly better INRT delineation without necessarily increasing radiation volumes.

Objectifs Evaluer les pratiques de radiotherapie dans la prise en charge des lymphomes de Hodgkin localises. Materiel et methodes A l’initiative d’un groupe pluridisciplinaire, TEP-RT-Hodgkin, un questionnaire centre sur les concepts de volumes cibles (nodal, involved field et involved site) et la TEP en position de traitement a ete envoye dans 35 centres academiques francais, par le biais de la Societe francaise de radiotherapie oncologique (SFRO). Resultats Vingt-huit centres (80 %) ont repondu, soignant moins de cinq patients par an pour 11 % d’entre eux, de cinq a dix pour 29 %, de dix a 20 pour 46 % et plus de 20 pour 14 %. Les oncologues radiotherapeutes avaient 19,0 ± 9,8 ans d’experience, dont 14,9 ± 10,1 dans la prise en charge des lymphomes de hodgkin, et 61 % d’entre eux avaient participe a l’essai H10. Quatre-vingt-six pour cent se disaient a l’aise avec les trois concepts. Quinze ont declare considerer le nodal comme un standard et l’utiliser en routine. Cinq ont repondu que l’involved field constituait le standard, hors essai. Huit recouraient a l’involved site. Cinquante pour cent des oncologues radiotherapeutes ayant participe a l’essai H10 pratiquaient le nodal en routine. A l’inverse, 50 % de ceux n’ayant pas participe a l’essai l’avaient instaure en traitement standard. Si tous utilisaient la tomographie par emission de positons (TEP) pour definir les volumes cibles, 19 realisaient des TEP en position de traitement. Trois avaient un acces difficile a cet examen et six pas d’acces. Dans cinq centres, les patients etaient referes apres chimiotherapie et donc sans possibilite de la realiser. Si la plupart a declare avoir une collaboration avec un medecin nucleaire, quinze oncologues radiotherapeutes se sont dits interesses par la creation d’un reseau de relecture des TEP. Conclusion Hors essai, la definition des volumes et l’acces a la TEP en position de traitement sont heterogenes. Afin d’harmoniser les pratiques, le groupe prepare des recommandations sur la realisation de la TEP et la prise en charge des patients.

The Hodgkin’s Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin’s lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin’s lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including 18fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin’s lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer with a poor prognosis. Locoregional staging is based on dynamic contrast-enhanced (DCE) CT or MRI. The aim of this study was to compare the performances of FDG PET/CT and DCE CT in locoregional staging of IBC and to assess their respective prognostic values.The study group comprised 50 women (median age: 51 ± 11 years) followed in our institution for IBC who underwent FDG PET/CT and DCE CT scans (median interval 5 ± 9 days). CT enhancement parameters were net maximal enhancement, net early enhancement and perfusion.The PET/CT scans showed intense FDG uptake in all primary tumours. Concordance rate between PET/CT and DCE CT for breast tumour localization was 92%. No significant correlation was found between SUVmax and CT enhancement parameters in primary tumours (p0.6). PET/CT and DCE CT results were poorly correlated for skin infiltration (kappa = 0.19). Ipsilateral foci of increased axillary FDG uptake were found in 47 patients (median SUV: 7.9 ± 5.4), whereas enlarged axillary lymph nodes were observed on DCE CT in 43 patients. Results for axillary node involvement were fairly well correlated (kappa = 0.55). Nineteen patients (38%) were found to be metastatic on PET/CT scan with a significant shorter progression-free survival than patients without distant lesions (p = 0.01). In the primary tumour, no statistically significant difference was observed between high and moderate tumour FDG uptake on survival, using an SUVmax cut-off of 5 (p = 0.7 and 0.9), or between high and low tumour enhancement on DCE CT (p0.8).FDG PET/CT imaging provided additional information concerning locoregional involvement to that provided by DCE CT on and allowed detection of distant metastases in the same whole-body procedure. Tumour FDG uptake or CT enhancement parameters were not correlated and were not found to have any prognostic value.

7509Background: The TMTV assessed on the baseline FDG-PET is a novel approach of tumor burden measurement. It has been reported to influence HL outcome in a retrospective series (Kanoun, EJNM 2014)...

The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by (18)F-FDG PET/CT.The study group comprised 22 patients with breast cancer (age 58 ± 11 years, mean ± SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 ± 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV(max) between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution.Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p0.0001).Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS.

Hybrid systems associating the sharpness of anatomic images coming from computed tomography (CT) and radionuclide functional imaging (SPET or PET) are opening a new era in oncology. This multimodal imaging method is now routinely used for the diagnosis, extent, follow up, treatment response and detection of occult disease in different types of malignancies with a significant impact on the treatment strategy leading for a change for more than 68% of all investigated patients.

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Neuroendocrine (NE) cancers are usually suspected on clinical symptoms related to their metabolically active peptide secretion into the circulatory system. The most effective treatment is surgery and a preoperative accurate localization of these slow growing tumors is needed. Combined anatomical (CT) and molecular imaging modalities using single-photon emission computed tomography (SPET) with radiolabeled pentetreotide have been developed in routine, and we report here the potential of SPECT/CT image fusion for diagnosis, staging, and evaluation of treatment efficacy of NE cancers.

Although radionuclide lymphoscintigraphy (RNL) is widely used diagnostically for patients with lymphedema (LE), it has not been utilized for LE staging, which is still based upon clinical findings. The aim of this work is to establish whether the results of both conventional RNL and fusion imaging obtained from hybrid detectors may be used for a comprehensive clinicoimaging staging in LE. Radiolabeled nanocolloids (0.2 ml) were subcutaneously injected in 4,328 patients (23-78 years) with clinical lower limb LE and without venous disease. Patients were classified according to the ISL classification and had a minimal follow-up of 2 years. Images were taken 60 minutes after the injection as a whole body scanning and fusion images of functional SPET and anatomical CT. Clinical and RNL results were not in accordance, and a specific RNL staging was established. The association of clinical and functional staging yields a new method to grade LE patients, and this staging correlated with treatment efficacy. RNL is an important tool in lymphology, and its association with the clinical evaluation offers a new grading system which may be able to delineate patients with good prognosis, patients at risk for a complex decongestive physiotherapy (CDP) failure, and patients who may benefit from other therapeutic protocols.

Item does not contain fulltext PURPOSE: To develop easily applicable guidelines for the determination of initially involved lymph nodes to be included in the radiation fields. PATIENTS AND METHODS: Patients with supra-diaphragmatic Hodgkin lymphoma. All the imaging procedures were carried out with patients in the treatment position. The prechemotherapy PET/CT was coregistered with the postchemotherapy CT simulation for planning purposes. Initially involved lymph nodes were determined on fused prechemotherapy CT and FDG-PET imaging data. The initial assessment was verified with the postchemotherapy CT scan. RESULTS: The classic guidelines for determining the involvement of lymph nodes were not easily applicable and did not seem to reflect the exact extent of Hodgkin lymphoma. Three simple steps were used to pinpoint involved lymph nodes. First, FDG-PET scans were meticulously analysed to detect lymph nodes that were overlooked on CT imaging. Second, any morphological and/or functional asymmetry was sought on CT and FDG-PET scans. Third, a decrease in size or the disappearance of initially visible lymph nodes on the prechemotherapy CT scan as compared to the postchemotherapy CT scan was considered as surrogate proof of initial involvement. CONCLUSIONS: All the radiological procedures should be performed on patients in the treatment position for proper coregistration. It is highly advisable that all CT and/or CT/PET scans be performed with IV contrast. Using the above-mentioned three simple guidelines, initially involved lymph nodes can be detected with very satisfactory accuracy. It is also emphasized that the classic guidelines (2, 3, 4) can always be used when deemed necessary.

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) represent 15 – 20% of all malignancies in children [1]. One of the major problems for clinicians is the presence of radiological or clinical res...

Objectifs Etudier la valeur de la reponse metabolique precoce apres un mois (M1) d’hormonotherapie neoadjuvante chez des patientes (pts) menopausees presentant un cancer du sein localement avance exprimant des recepteurs hormonaux. Analyser la valeur pronostique de la reponse metabolique precoce sur les parametres de survie (survie globale OS et survie sans metastases a distance DFMS). Patients et methodes Il s’agissait d’une etude prospective ancillaire de l’essai clinique CARMINA 02 comparant l’efficacite de l’anastrozole et du fulvestrant en neoadjuvant pendant 4 a 6 mois. Les pts etaient considerees comme « repondeuses metaboliques » precoces (mR) en cas de diminution du SUVmax de la tumeur mammaire ≥ 40 % a M1 ou « non-repondeuses metaboliques » (mNR) sinon. La reponse metabolique preoperatoire a egalement ete evaluee. La reponse metabolique precoce a ete comparee aux reponses morphologiques (clinique et IRM), histologique selon le score de Sataloff, a l’evolution de l’expression du Ki 67, mais aussi a l’OS et a la DFMS. Resultats Cinq pts sur 11 (74,2 ans ± 3,6) etaient mR a M1 (−57,5 % ± 11,9 mR vs −16,7 % ± 10,2 mNR ; p = 0,00017), avec une reponse metabolique preoperatoire persistante (−63,6 % ± 25,6 mR vs −30 % ± 16,1 mNR ; p = 0,018). Il existait une diminution de la taille tumorale clinique (26,2 % ± 14,1 mR vs −8,3 % ± 26,4 mNR ; p = 0,21) et IRM (−33,6 % ± 22,36 mR vs −18 % ± 21,2 mNR ; p = 0,27) plus importante mais non significative en preoperatoire dans le groupe mR. La seule patiente en reponse metabolique complete preoperatoire a presente la meilleure reponse histologique (Sataloff TB). L’expression du Ki 67 etait plus faible a M1 chez les pts mR, bien que non significative (3,6 % ± 1,9 mR vs 8,2 % ± 8 mNR ; p = 0,25). Meme si aucune difference de survie n’a pu etre mise en evidence pour l’OS ( p = 0,32) et la DFMS ( p = 0,2) entre les deux groupes, un deces lie a la progression et 2 progressions metastatiques ont eu lieu dans le groupe mNR. Conclusion Ces resultats preliminaires montrent l’interet de la reponse metabolique precoce a l’hormonotherapie neoadjuvante par rapport a la reponse morphologique et peut-etre un meilleur pronostic des patientes mR.

Purpose Initial lymphoma staging requires bone marrow assessment in aggressive lymphomas. Bone marrow lymphoma infiltration is routinely assessed by bone marrow biopsy (BMB), considered as the “gold standard”. The aim of this study was to compare the performance of BMB, whole-body MRI and PET/CT for evaluation of BM infiltration. Methods Patients with newly diagnosed aggressive lymphoma were evaluated by BMB, MRI and PET/CT. Two radiologists, two nuclear medicine physicians and one pathologist independently assessed the results of the three modalities. Bone was considered as involved if BM was positive or if PET/CT or MRI was positive and if there was a resolution of the abnormal image shown on PET/CT or MRI halfway or at the end of therapy. Results Both MRI and PET/CT detected bone marrow lesions in the 9/43 patients, but two patients with multiple lesions had more lesions detected by PET/CT compared to MRI. Among these nine patients, two with an iliac crest lesion detected by both MRI and PET/CT had bone marrow involvement with large-cell lymphoma on histological examination. The other seven patients had focal MRI and PET/CT lesions in areas other than the iliac crest, where the blind BMB was done. The other patients had bone marrow without large-cell lymphoma involvement. In all cases, after lymphoma therapy bone marrow involvement regressed on histological examination, PET and MRI. Conclusion These preliminary results suggest that non-invasive morphological procedures could be superior to BMB for bone marrow assessment in aggressive lymphomas. Ongoing study is underway to validate these results.

This review focuses on imaging of osteosarcoma and Ewing's sarcoma of the long bones in children during preoperative neoadjuvant chemotherapy. Morphological criteria on plain films and conventional static MRI are insufficiently correlated with histological response. We review the contribution of dynamic MRI, diffusion-weighted MR and nuclear medicine (18FDG-PET) to monitor tumoural necrosis. MRI is currently the best method to evaluate local extension prior to tumour resection, especially to assess the feasibility of conservative surgery. Quantitative models in dynamic MRI and 18FDG-PET are currently being developed in order to find new early prognostic criteria, but for the time being, treatment protocols are still based on the gold standard of histological response.

Abstract 2817 Background: The INRT concept, that limit delineates irradiated volume to lymphoma-infiltrated node, requires an extremely precise determination of the number and volume of initially involved nodes. In the study, we tried to assess the additional value of a PET/CT performed before treatment. Patients and methods: Early-stage lymphoma patients entered in the EORTC-GELA-IIL. Data imaging comprising PET/CT prior to treatment and CT simulation prior to radiotherapy were retrieved using the DICOM/DICOM-RT imaging network connecting all French cancer centers participating in the H10 trial. A lymph node was considered to be involved if it fulfilled 3 requirements: FDG uptake was greater than the background, was clearly identifiable on CT, and either decreased or disappeared after chemotherapy. Involved lymph nodes were delineated on CT first before adding the information provided by PET. Differences between the number of involved lymph nodes and areas were compared before and after PET/CT assessment. Results: From March 2007 to February 2010, 117 patients from 18 French Cancer Centers and hospitals were included in the study. PET/CT identified at least one additional FDG-avid lymph node in 82/117 patients (70%; CI 95%: 61–78%). Additional lymph nodes were observed significantly (p = 0.008) more frequently when PET/CT was performed without IV contrast (in 79% of the patients versus 56%). At least one additional lymph node area was detected by PET in 49/117 patients (42%; CI 95%: 33–51%). There was a 15% (CI 95%: 9–22%) increase in the gross target volume (GTV) due to the additional information provided by PET (a 20% increase in 10% of the patients). On the other hand, after chemotherapy, there was a 10% (CI 95%: 5–18%) increase in the clinical target volume (CTV) in the 96 assessable patients (a 20% increase in 10% of the patients). Conclusions: PET/CT with IV contrast may be an important imaging procedure for implementing the INRT concept. Disclosures: Ribrag: LFB: Honoraria, Research Funding; servier: Research Funding; celgene: Research Funding; pfizer: Honoraria; novartis: Honoraria.

Intra-arterial hepatic chemotherapy is effective in the treatment of liver metastases, and it has been used at the Gustave Roussy Institute since 1983. During laparotomy, arterial catheters are introduced usually into the gastroduodenal artery, and they are connected either to a subcutaneous access or to an implantable pump. Seventy-one patients with liver metastases from colorectal adenocarcinoma were examined by angioscintigraphy to evaluate the quality of liver perfusion. Our technique uses three radioactive compounds and makes it possible to obtain a standard liver scintigram with technetium 99-colloidal rhenium sulphur, a dynamic view of liver arterial perfusion by injection of pure technetium 99 pernechtate, and a static mapping of well-perfused territories after injection of technetium 99-labelled macroaggregated albumin. This technique is reliable to explain most of the problems encountered during intra-arterial hepatic chemotherapy. In our experience, the quality of perfusion was highly variable and had a prognostic value. Objective responses were more frequent in well-vascularized metastases (64 percent) than in metastases with hypoperfusion (36 percent). Survival was also better in the former case, with a median survival of 18 months as against 12 months (p = 0.028).

BACKGROUND Escalated BEACOPP (BEAesc) demonstrated a better disease control than ABVD but no overall survival (OS) improvement in patients with advanced Hodgkin Lymphoma (HL) (Federico et al , J Clin Oncol 2009, Viviani et al, N Engl J Med 2011, Mounier et al, Ann Oncol 2014). The superior efficiency of BEAesc is associated to a substantially higher immediate hematological toxicity, and an increased risk of secondary myelodysplasia/leukemia and infertility. So, to better manage HL treatment there is a need to identify early responding patients able to benefit from a strategy of dose intensity de-escalation after upfront BEAesc, without impairing the disease control. PET performed after 2 cycles of chemotherapy (PET2) might identify such a population suitable for receiving ABVD after 2 cycles of upfront BEAesc, and was implemented in the present study. METHODS The AHL 2011 trial (NCT01358747) was designed to evaluate in 16 to 60 years old HL patients with Ann Arbor stage III, IV or high risk IIB, a treatment strategy driven by PET after 2 BEAesc cycles (PET2), delivering 4 cycles of ABVD for PET2 negative patients and 4 cycles of BEAesc for PET2 positive patients. This PET-driven strategy was randomly compared to a standard treatment not monitored by PET and delivering 6 cycles of BEAesc. A baseline PET was mandatory before treatment and PET2 were centrally reviewed and interpreted according to Deauville criteria within 48 hours. The allocation of treatment in the experimental arm was based on the PET2 central review results. PFS was the primary endpoint of the study with a hypothesis of non-inferiority of the PET driven arm compared to the standard arm with a margin of 10% (85% 5y-PFS in the standard arm vs >75% in the PET driven arm). An interim analysis of the primary endpoint was planned after 50% (n = 49) of the 97 scheduled events needed for the final analysis. RESULTS From May 2011 to May 2014, 823 patients were registered and 782 were eligible for the interim analysis including 401 patients in the arm A, and 381 in arm B. Patients characteristics were well balanced in both arms: median age was 30 years (16 - 60), 64% were male, 81% had nodular sclerosis and 12% mixed cellularity HL, 12% had stage IIB, 28% stage III, 60% stage IV, and 58% had an international prognosis score ≥3. After 2 cycles of BEAesc PET was positive in 97 (12%) patients and PET2 positivity was similar in the standard and experimental arms (n = 48, 12% and n = 49, 13% respectively). Based on PET2 results, 319 (84%) patients received 4 cycles of ABVD and 49 (13%) 4 additional cycles of BEAesc in the experimental arm. Grade ≥3 toxicity was significantly higher in patients receiving 6 cycles of BEAesc compared to those who received 2 cycles of BEAesc + 4 cycles of ABVD with more frequent anemia (11% vs 2%), leukopenia (85% vs 72%), thrombocytopenia (44% vs 13%), febrile neutropenia (6% vs 3%), and sepsis (7% vs 4%). 182 serious adverse events (SAE) related to treatment occurred in 108 (24%) patients treated with 6 cycles of BEAesc (leading to death in 4 cases), compared to 72 SAE (leading to death in 1 case) in 50 (15%) patients treated with 2 x BEAesc + 4 x ABVD (p With a median follow up of 16.3 months, in an intent to treat basis, the estimated 2y-PFS was similar in the standard (91.6%) and the PET driven arms (88.3%; p = 0.79). PET2 positivity was related to a significantly lower 2y-PFS compared to PET2 negative patients in the whole population (72.9% vs 92.8%; p CONCLUSIONS This interim analysis suggests that PET performed after 2 cycles of BEAesc can be safely used to guide subsequent treatment and supports the response-adapted strategy delivering 4 cycles of ABVD for patients with negative PET2 (84%) without impairing the disease control. This approach allows to significantly reduce the treatment-related immediate toxicity in most patients and provides similar patients' outcome compared to standard BEAesc treatment. Still, PET positivity after 2 cycles of BEAesc is related to a higher risk of disease progression, encouraging to develop new treatment options in patients with PET2 positive advanced stage HL. Disclosures Casasnovas: Roche: Consultancy, Research Funding; Takeda: Consultancy; Gilead: Consultancy. Salles:Celgene Corporation; Roche and Gilead Sciences: Research Funding; Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy; Celgene Corporation; Roche: Speakers Bureau. Dupuis:ABBVIE: Membership on an entity's Board of Directors or advisory committees; ROCHE: Speakers Bureau. Morschhauser:Genentech Inc./Roche: Other: Advisory boards. Tempescul:Gilead: Other: Export Board Committee.

TPS8615 Background: ABVD is the most widely chemotherapy regimen used as standard treatment of advanced Hodgkin lymphoma (HL). The escalated BEACOPP (BEAesc) regimen which delivers more drugs at higher dose intensity was shown to improve patient’s PFS but not OS when compared to ABVD (Federico M, 2009; Viviani S, 2011; Carde P, 2012). The better efficiency of BEAesc is associated to a marked immediate hematologic toxicity and a higher risk of secondary myelodysplasia/leukemia. Also, the gonadal toxicity which is a real concern in young women, is quite higher when using BEAesc. So, to better manage HL treatment we need to identify early responding patients able to benefit from a strategy of dose intensity decrease after upfront BEAesc, without impairing the disease control. PET performed after 2 cycles of chemotherapy (PET2) might identify such a population suitable for receiving ABVD after 2 cycles of upfront BEAesc, and was implemented in the present study. Methods: The AHL 2011 trial (NCT01358747) was designed to test in 16 to 60 years old HL patients with Ann Arbor stage III, IV or high risk IIB, a treatment strategy driven by PET after 2 cycles of BEACOPPesc, delivering 4 cycles of ABVD for PET2 negative patients and 4 cycles of BEAesc for PET2 positive patients, compared to a treatment not monitored by PET, delivering the best BEAesc schedule consisting in 6 cycles of this regimen (Engert A, 2012). A baseline PET is mandatory before treatment and PET2 are centrally reviewed within 48 hours and interpreted according to Deauville criteria. The allocation of treatment in the experimental arm is based on the PET2 central review result. PFS is the primary endpoint of the study with an hypothesis of non-inferiority of the experimental arm with a margin of 10% (85% 5y-PFS in the control arm vs >75% in the experimental arm). With a 6-year of accrual period, inclusion of 405 patients in each arm would have 80% power to detect a HR of 1.77 using a one-sided log rank test with significance level of 0.025. The trial started in May 2011 and to date, 385 patients have been enrolled. The DSMC reviewed the trial in November 2012 and suggested that the trial continue as planned. Clinical trial information: NCT01358747.

Advances in the management of neuroblastoma lead radiologists and nuclear medicine specialists to optimize their procedures in order to propose a rational use of their techniques, adjusted to the various clinical presentations and to therapeutic management. The aim of this paper is to assess the imaging procedures for the diagnosis and follow-up of neuroblastoma in children according to current therapeutic European protocols. An imaging strategy at diagnosis is first proposed: optimal assessment of local extension of the primary tumour is made with MRI, or spiral-CT when MRI is not available, for all locations except for abdominal tumours for which CT remains the best imaging modality. Metastatic extension is assessed with mIBG scan and liver sonography. Indications for bone metastasis evaluation with either radiological or radionuclide techniques are detailed. Imaging follow-up during treatment for metastatic or unresectable tumours is described. A check-list of radiological main points to be evaluated before surgery is proposed for localized neuroblastoma. The imaging strategy for the diagnosis of "occult" neuroblastoma is considered. Finally, we explain the management of neuroblastoma detected during the prenatal or neonatal period.