Rationale: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. Patients and methods: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m(2) and CDDP 100 mg/m(2) on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie <= 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. Results: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. Conclusion: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.

Introduction > Patients with liver metastasis from uveal melanoma have a poor prognosis. Efficacy and safety of hepatic transarterial chemoembolization (TACE) using melphalan and microspheres was evaluated. Materials and methods > Monocentric retrospective study of all consecutive patients treated by TACE using melphalan and 2504m calibrated microspheres between 2004 and 2016. Radiological response was assessed according to RECIST 1.1, modified (m)-RECIST and EASL on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The primary endpoint was overall survival (OS). Liver metastasis response, hepatic, extrahepatic and global progression free survival (PFS) complications were evaluated with the common terminology criteria for adverse events version 4.0 (CTCAE 4.0) and survival factors were secondary endpoints. Results > Thirty-four patients underwent 138 TACE (4; 4.1 sessions; range 1-9). Median OS was 16.5 months (mean 21.6 months). Liver metastasis response combining partial and complete response was 42.4%, 97%, 97% with RECIST 1.1, mRECIST, EASL, respectively. There were 58 severe (CTCAE >= 3) but manageable complications in 28 patients, except for 1 toxic death. Conclusion > For patients with liver metastases from uveal melanoma ineligible for local treatments, TACE using melphalan may be performed as first line therapy in metastatic miliary disease from uveal melanomas with careful supportive care.

8029 Background: Hodgkin Lymphoma (HL) treatment in the elderly is a challenge, as standard ABVD is able to cure no more than 60% of the patients (p.). Bendamustine (Be), and Brentuximab Vedotin (BV), are well-tolerated and effective drugs in relapsing HL, but only preliminary data exist in 1st line treatment of the elderly (Evens AM 2018). Methods: HALO is a prospective international multicenter open-label phase I/II study (NCT02467946) to assess the safety and efficacy of Be-BV in advanced-stage elderly HL p. Briefly, BV 1.2 mg/kg on D1, and Be 90 mg/m2 on D1-2 were administered Q3W for 6 cycles. The primary endpoint was the feasibility and the efficacy of Be-BV. Results: Between July 2015 and February 2019, 59/60 p. consecutive enrolled received at least 1 Be-BV cycle, and are valuable for primary endpoint. One p. was excluded because a histological review showing angioimmunoblastic T-Cell Lymphoma. The mean age was 70.32 (62-79), and M/F ratio 41/18. The Ann-Arbor stage was IIB in 12, III in 14 and IV in 33 patients, B-symptoms (y/n) 40/19. IPS was 0-2 in 19 and ≥ 3 in 40 p., P.S. (ECOG) was 0-1 in 53, 2 in 6 p., nonetheless most of them were frail, as ADL was ≥ 6 in 47 (79%) and IADL was ≥ 8 in 42 (71%) p. Most frequent co-morbidities were cardio-vascular disease (45) metabolism disorders (31) prostatic adenoma (11). 163 treatment-related adverse events (WHO 3-4) were recorded: neutropenia and lymphopenia, (134), infections (7), cutaneous reactions (5), liver toxicity (2). No case of grade > 2 peripheral neuropathy was recorded. Out of 59 p., 41 concluded and 18 interrupted the treatment for toxicity (8), progression (5), treatment failure (2), CMV reactivation (3). The latter was recorded in 17 p., 12/17 received valgancyclovir. 4 p. died with CMV viremia. After a mean follow-up of 20.6 (0.3-46.5) months, 37/59 (63%) were in CR, while 22 (37%) have progressed (5) or relapsed (17). The 2-y OS and PFS in ITT analysis were 83% (95% CI 71-96) and 54% (95% CI 41-72) and in PP 89% (95%CI 75-100) and 78% (95%CI 64-96), respectively. 22 p. had a PFS event: 5 progression (2 deaths), 17 relapse (8 deaths). 10 p. died for recurrent HL (5), sepsis (1), secondary malignancy (2), respiratory insufficiency (1) and unknown (1). Conclusions: The Be-BV combination, a novel anthracycline-free regiment for first line treatment of HL in elderly, proved effective in unselected, frail, poor-risk, HL p. aged more than 60 in daily hospital real life. The CMV reactivation is frequent and should be treated with preemptive antiviral therapy upon detection of CMV DNA in plasma. Clinical trial information: NCT02467946 .

Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of human cancers. While the highest incidence of sarcomas is observed in elderly, this population is often excluded or poorly represented in clinical trials. The present study reports on clinicopathological presentation, and outcome of sarcoma patients over 90 recorded in the Netsarc.org French national database. NETSARC ( netsarc.org ) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor board (MDTB), funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB, second pathological review, and collection of sarcoma patient characteristics and follow‐up are collected in a database Information of patients registered from January 1, 2010, to December 31, 2016, in NETSARC were collected, analyzed and compared to the younger population. Patients with sarcomas aged >90 have almost exclusively sarcomas with complex genomics (92.0% vs . 66.3%), are less frequently metastatic (5.3% vs . 14·7%) at diagnosis, have more often superficial tumors (39.8% vs . 14.7%), as well as limbs and head and neck sites (75.2% vs . 38.7%) (all p < 0.001). Optimal diagnostic procedures and surgery were less frequently performed in patients over 90 ( p < 0.001). These patients were less frequently operated in NETSARC centers, as compared to those of younger age groups including aged 80–90. However, local relapse‐free survival, metastatic relapse‐free survival and relapse‐free survival were not significantly different from those of younger patients, in the whole cohort, as well as in the subgroup of operated patients. As expected overall survival was worse in patients over 90 ( p < 0.001). Patients over 90 who were not operated had worse overall survival than younger patients (9.9 vs . 27.3 months, p < 0.001). Patients with STS diagnosed after 90 have distinct clinicopathological features, but comparable relapse‐free survival, unless clinical practice guidelines recommendations are not applied. Standard management should be proposed to these patients if oncogeriatric status allows.

PURPOSE:To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS:Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS:Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION:WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

INTRODUCTION:Distant metastases of papillary thyroid cancers are rare. Most common metastatic sites include bone and lung, whereas metastases to brain, eye, breast, liver, kidney, muscle, and skin are infrequent and almost always appear in advanced-stage tumor disease. Metastases to ovary and/or uterus are even scarcer. We report herein a very exceptional case of asymptomatic malignant-to-benign tumor-to-tumor metastasis of thyroid origin into a uterine leiomyoma.CASE PRESENTATION:We present the case of a 53-year-old female patient who had a previous history of pT1b N0 M0 R0 papillary carcinoma of the lower left thyroid lobe, treated by total thyroidectomy and central lymph node dissection and two successive administrations of radioactive treatment with iodine-131. Six years later, follow-up imaging disclosed an asymptomatic slow-growing 40-mm-long pedicled subserous heterogeneous uterine myoma including a 12-mm hypervascular nodule, which was suspicious for thyroid malignancy on MRI.DISCUSSION:Histopathology of a hysterectomy specimen disclosed a hypervascular well-limited poorly differentiated trabecular carcinomatous infiltration within the uterine leiomyoma. The immunohistochemical profile of the suspicious nodule was compatible with a thyroid origin.CONCLUSION:A hypervascular "hot spot" intramyoma nodule was the diagnostic clue in a clinical context of hematogenous tumor spread of thyroid origin (increased thyroglobulin level).

FDG-PET/CT (PET) is now considered the standard imaging tool for Hodgkin Lymphoma (HL) staging and restaging. However a CT-detected residual mass at the end of therapy (EoT) is still a challenge for PET interpretation. The aim of our study was to improve the overall accuracy of EoT PET/CT by using a dynamic dual-point scanning at 60 and 120 after FDG injection (2P-PET/CT). Fifty-one HL patients showing a single residual FDG-avid mass (SFAM) at EoT PET/CT were included in the study in Italy and Poland. Treatment was ABVD, ABVD followed by BEACOPP or ABVD plus radiotherapy. Only patients with a SFAM and a Deauville score (DS) > 2 in EoT PET/CT were included in the study. Two independent nuclear medicine reviewed images with a semi-quantitative analysis (SUVMax and retention index, RI) and a visual scoring according to DS. Compared to standard PET, 2P-PET/CT showed only a modest increase in NPV and PPV, from 0.87 to 0.89 and of the PPV from 0.67 to 0.71, respectively. Increase of the overall accuracy became substantial upon including in the analysis only patients whose images were acquired in strict adhesion to original protocol of 2P-PET/CT scanning: (t 120'-6040 min): the sensitivity increased from 0.60 to 1.00, PPV from 0.75 to 0.83 and NPV from 0.89 to 1. This study, with caution for the small number of patients included, seems to suggest that 2P-PET/CT could increase the overall accuracy of EoT PET/CT in correctly classifying treatment response in HL with a persisting SFAM at EoT.

11523 Background: the benefit of neo-adjuvant/adjuvant chemotherapy (CT) in rare bone sarcoma is poorly documented. Methods: retrospective study from the French sarcoma network for bone tumors ResOs: 1) adult patients (pts) from 1976 to 2014, 2) Rare bone sarcoma: leiomyosarcoma, undifferentiated pleomorphic and radiation-associated bone sarcoma 3) with central pathological review. Clinical features, treatment modalities and outcome were recorded and analyzed. Results: we identified 149 pts from 14 centers. Of them, 109 (73%) presented with localized disease, the local treatment was associated or not with CT. In localized pts, median age was 53 (range 18-82) years (y), median tumor size was 7cm (range 3-18). Sites of disease were extremities (72%) or axial skeleton (28%). The most common histological subtypes were high-grade leiomyosarcoma (33%) and undifferentiated pleomorphic sarcoma (35%). Surgery was performed in 107 pts, conservative in 76.3%. R0 resection was achieved in 58 (82%) pts. Twenty-eight pts (26%) underwent upfront surgery or exclusive radiotherapy (RT)( > 50 Gy) without CT. Eighty-one pts (74%) received either neo-adjuvant CT (n = 13) or adjuvant CT (n = 23) or both (n = 45). The median duration of neo-adjuvant CT was 2.1 months (mo)(range: 0.1-5.7) and 2.4 mo for adjuvant CT (range: 0.7-6.4). Neo-adjuvant/adjuvant CT was mostly doxorubicin- (95%/85%) and cisplatin- (68%/63%) based, or methotrexate-based in 22%/21% of pts. Adjuvant RT was performed in 23 (22%) pts. An overall disease control rate (CR+PR+SD) of 86% was achieved after neo-adjuvant CT. Median follow-up was 5.6 y (95% CI 4.0-7.8). For patients with localized disease, the 3y and 5y-overall survival (OS) were 74.3% (95% CI: 64.1-82.0) and 62.4% (95% CI: 50.7-72.1). The 3y- and 5y-disease-free survival (DFS) were 52.5% (95% CI: 42.1-61.9) and 38.2% (27.7 and 48.5). In univariate analysis, age≤50y (p = 0.04) and neoadjuvant and adjuvant CT (p = 0.03) were associated with longer DFS, but no association was found with OS. Conclusions: in this retrospective study, patients with localized rare bone sarcoma treated according osteosarcoma standard of care, with pre- and post-operative chemotherapy, achieved better DFS.

11501 Background: DT are a group of locally aggressive tumors of fibroblastic origin that can lead to significant morbidity. No randomized trial assessing systemic treatment activity in this rare disease has been reported previously. Methods: DESMOPAZ is a multicenter non-comparative randomized phase II trial based on a two-stage optimal Simon's design assessing safety and efficacy of PZ in DT adult patients (pts). All pts had to have documented progressive disease (PD) according to RECIST 1.1 based on two imaging within a 6-months interval. Pts were randomly assigned to receive PZ 800 mg/day orally continuously, or M (30 mg/m²) + V (5mg/m²) intravenously once a week for 6 months and then every 15 days for 6 months. Treatment was administered until PD (cross-over then permitted), unacceptable toxicity, and for a maximum of 1 year. The primary endpoint was 6-month non-PD rate according to RECIST 1.1. Based on the following hypotheses: P0 = 60%, P1 = 80%, α = 5% and β = 20% and a 2:1 randomization, a total of 43 assessable pts were needed in PZ-arm and 22 pts in MV-Arm. PZ could be regarded as an active drug if at least 31/43 6-month non-PD. Archive FFPE samples of tumor tissue were mandatorily collected at baseline, and an on-treatment tumor biopsy at Cycle 2 was optional. Results: Accrual started in September 2012 in 12 centers of the French Sarcoma Group. As of December 2017, 72 pts (26 males, 46 females) were included: 48 in PZ-arm (46 assessable) and 24 in MV-arm (20 assessable). Median age was 40 years (18-79). The median number of previous lines of treatment was 1 (0-3). After central pathological and radiological review, 38 assessable pts (82.6%) in PZ-arm had tumor shrinkage, resulting in PR in 17 (37%) and SD in 21 (45.7%). In MV-arm, 11 assessable pts (55%) has tumor shrinkage resulting in PR in 5 (25%) and SD in 6 (30%). The 6-month non-PD rate was 86% (95%CI = 72.1-94.7) in PZ-arm (37/43) and 50% (95%CI = 27.2-72.8) in MV-arm (10/20). Conclusions: The primary endpoint of the DESMOPAZ study was reached. PZ has meaningful clinical activity in pts with progressive DT. Safety, quality of life and pharmacodynamics translational data will be presented at the meeting. Clinical trial information: NCT01876082.

11504 Background: Oral multikinase inhibitor REG has shown activity in GIST and non-adipocytic soft tissue sarcomas. We designed REGOBONE as a non-comparative phase II, double-blind, PL-controlled trial to study the efficacy and safety of REG for pts with metOS and other types of bone sarcomas. This trial consisted of 4 independent cohorts : metOS, Ewing sarcoma, chondrosarcoma, and chordoma. We report here the metOS cohort results. Methods: metOS pts were randomized (2:1) to receive either REG (160 mg/d, 21/28d) or PL with optional cross-over at the time of confirmed central review of progressive disease (PD). Key-eligibility criteria were age ≥10 years, histologically confirmed diagnosis of OS, confirmed measurable PD not amenable to curative-intent, 1-2 previous chemotherapy (CT) regimen(s) for metastatic disease, and ECOG 0-1. 24 pts were planned in the REG arm based on A’Hern’s single-stage design for phase II trials (1-sided α = 0.05, and 80% power) to detect a 27% benefit in the progression-free rate at 8 weeks (P0 = 40%). Major secondary endpoints were PFS (per modified RECIST1.1), OS and safety. Results: From June 2014 to April 2017, 43 metOS pts were included. Five pts were not eligible for efficacy analysis. Of 38 efficacy-evaluable pts (12 in PL arm and 26 in REG arm) ; 24 were men, median age was 33 (18-74) years, 28 (74%) had 1 previous CT regimen. 17 pts (65.4% ; one-sided CI95% = [47.4%-]) were non-progressive at 8 weeks in the REG arm vs. 0 in the PL arm. Median PFS was 13.7 (CI95% = 8.0-27.3) vs. 4 (CI95% = 3.0-5.7) weeks for REG and PL arms, respectively. PFS rate at 24 weeks was 35% (CI95% = 17-52) in the REG arm vs. 0 in the PL arm. 1-year OS was 53% (CI95% = 31-71) and 33% (CI95% = 10-59) for REG and PL arms, respectively. Ten pts crossed-over to REG after centrally-confirmed PD on PL. The most common ≥Gr3 REG-related AEs during the double blind period were hypertension (24%), hand-foot skin reaction (17%), asthenia (10%) and diarrhea (7%). Conclusions: REG demonstrates very promising activity, with acceptable toxicity, in metOS after failure of conventional chemotherapy, justifying confirmatory trials. Clinical trial information: NCT02389244.

To evaluate the effectiveness and feasibility of high-intensity focused ultrasound (HIFU) for the treatment of bone metastases.

The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune‐like syndromes.

Four cycles of ABVD followed by 30Gy involved site radiotherapy (ISRT) is the standard of care in unfavourable classical Hodgkin lymphoma (HL). Since dose-density might represent an important factor to achieve complete remission and longterm survival, we designed a trial to evaluate dose-dense ABVD (ddABVD) in ptinents (pts) with early unfavourable HL. This prospective, multicentric, phase 2 study enrolled pts aged 18–70 years with newly diagnosed cHL, unfavourable stage I or II (EORTC criteria). Stage IIB bulky were excluded. Aims of the study were feasibility, safety and efficacy of ddABVD. DdABVD consists of Doxorubicin, Bleomycin, Vinblastine and Dacarbazine used at the same doses of conventional ABVD but is administered on days 1 and 8 every 3 weeks instead of days 1 and 15 every 4 weeks. In the absence of progressive disease (PD) or unacceptable toxicity, 4 cycles of ddABVD followed by ISRT were administered. Interim PET was mandatory after 2 courses (PET2). Pts experiencing PD were shifted to second-line therapy. Feasibility and activity of ddABVD were the primary endpoints of the study. By design, the study was considered feasible if ≤5 out of 52 pts required a dose reduction below 85% of the planned dose. The percentage of PET2 negativity was chosen as the parameter to evaluate its activity. Between Feb 2012 and Jun 2015, 96 pts were enrolled and evaluated. The feasibility endpoint was achieved with only 4 out of 52 pts requiring a dose reduction greater than 15%. The mean dose intensity in the 96 pts who started ddABVD treatment was 93.7% with only 3 pts unable to complete ddABVD due to toxicity. The activity analysis was performed in all 96 pts. PET-2 was available for 92/96 (95.8%) pts: 79 were PET2 negative (85.9%) and 13 PET2 positive (14.1%). In 4 pts PET2 wasn't performed (3 logistic reasons, 1 switched to standard ABVD due to a SAE at cycle 1). Considering the global outcome of the 96 pts who received at least 1 ddABVD course: 90 pts achieved CR (93.8%), 1 PR (1%), 4 PD (4.2%) and 1 (1%) was without a known disease assessment. With a median followup of 39.9 months (2.157.6), median PFS and OS were not reached, at 24 months PFS and OS were 91.5% and 97.9%. No statistically significant differences were observed for PET2 negative and PET2 pts for both 2 years PFS (94.9% vs 84.6%, p:0.260) and OS (98.7% vs 100% a, p:0.560). Most frequent toxicities were haematological. The infection rate was low (infection 8.3% and febrile neutropenia 6.25%); no patient developed cardiac toxicity until now. There was 1 toxic death after cycle 4; 3 pts were discontinued due to toxicity and were switched to standard ABVD or AVD. The study demonstrates the feasibility of ddABVD in early unfavourable cHL which also allows a reduction in overall treatment duration without a significant increase in toxicity. The dosedense strategy translated in excellent outcome in term of CR rate, PFS, OS with a low rate of PR at 2 years. DdABVD deserves further comparison with conventional ABVD.

Purpose: For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584).Patients and methods: Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age >= 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio >= 0.35, erythrocyte sedimentation rate (ESR) >= 50 without B-symptoms or ESR >= 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPPbaseline-IFRT (n = 255).Results: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPPbaseline-IFRT (5-year EFS, 88.8%) were not inferior to 6-ABVD-IFRT (5-year EFS, 89.9%): difference of 4.0% (90% CI, -0.7%-8.8%) and of 1.1% (90% CI,-3.5%-5.6%) respectively. The 5-year overall survival estimates were 94%, 93%, and 93%, respectively. Patients treated with combined modality treatment chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vincristine (Oncovin), cyclophosphamide, procarbazine, etoposide and prednisone (BEACOPP) baseline more often developed serious adverse events requiring supportive measures and hospitalisation compared with patients receiving the chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD).Conclusions: The trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPP(baseline) were more toxic than four or six cycles of ABVD. (C) 2017 Elsevier Ltd. All rights reserved.

Discussion | Although narrow-band UV-B phototherapy is the most widely used treatment modality for patients with vitiligo, it is associated with unnecessary UV exposure to normal skin.3 Because a majority of patients have limited involvement of their body surface, targeted phototherapy including a 308-nm xenon chloride excimer laser (EL) has been considered the treatment of choice for localized vitiligo.4 In this study, we observed a marked response using a 311-nm TSL to treat patients with nonsegmental vitiligo on the face and neck. The initial response was fast, and the overall efficacy of the TSL treatment was comparable to that reported for EL treatment.5 The therapeutic mechanism of TSL would involve immune modulation and melanocyte stimulation, as in narrow-band UV-B and EL treatment.6 The 311-nm TSL has several advantages. It does not require the periodic gas charging that is crucial for EL maintenance. In addition, the 311-nm wavelength of TSL can penetrate deeper than the 308-nm wavelength of EL. The gain-switched 311-nm TSL is a promising option for treating vitiligo. Further research is needed, including clinical trials comparing EL and TSL.

Abstract Background Despite a significant improvement of therapeutic results with the current immuno-chemotherapies, a consolidation treatment is still required for decreasing the risk of relapse. WBRT has been the historical standard consolidation in PCNSL patients, but IC + HCR has shown encouraging results in non-controlled studies. However, each procedure exposes patients to specific side effects, such as cognitive dysfunctions and treatment-related mortality, respectively. In this trial, we addressed the efficacy and toxicity of a standard chemo-immunotherapy followed by either WBRT or IC+HCR in first-line treatment of PCNSL patients. Methods Immuno-competent patients (aged 18-60) with newly diagnosed PCNSL and measurable disease were enrolled from 23 French centers. All the patients received 2 cycles of R-MBVP (Rituximab 375 mg/m2 D1, Methotrexate 3 g/m2 D1 and D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, Prednisone 60 mg/kg/D D1-D5) followed by 2 cycles of R-AraC (Rituximab 375 mg/m2 D1, Cytarabine 3g/m2 D1-D2) as induction chemotherapy. Participants were stratified upfront according to performance status (0-1 vs 2-4) and treating institution and randomly assigned (1:1)to receive either WBRT (Arm A) or IC + HCR (Arm B) as a consolidation treatment. IC consisted in thiotepa (250 mg/mg/m2/d days-9 through-7, busulfan 10 mg/kg (total dose) days-6 through -4, and cyclophosphamide 60 mg/kg/d days -3 and -2). Prospective neuro-cognitive evaluations were planned in both arms. Responses were assessed according to the IPCG criteria. A central review of MRIs was scheduled. The primary end-point was the 2-year progression free survival (PFS). Thirty-eight assessable patients who received the complete study treatment for each treatment were needed. Either of the two arms would be deemed effective if > 24/38 patients are free of disease at 2 year with no major side effects. Analysis was intent to treat, in a non-comparative phase 2 trial design.This study is registered with ClinicalTrials.gov, number NCT00863460. Results Between Oct 2008 and Feb 2014, 140 patients (male: 101; female: 39) were recruited (median age = 55 years, range 22-60) and randomized in Arm A (n=70) or Arm B (n = 70). Sixty-seven patients were assessable in each arm. Two patients withdrew their consent during the induction cycles (Arm A: n = 1; Arm B: n = 1). After two cycles of R-MBVP, overall response rates were 82% (CR + uCR = 24 %) and 77 % (CR + uCR = 23 %) in arm A and arm B respectively. At the end of the induction chemotherapy, ORR was 74 % (CR+ uCR = 44 %) and 67 % (CR+ uCR = 42 %) in arm A and B respectively. WBRT was given to 53 patients in arm A and IC+HCR was given to 44 patients in arm B. After consolidation treatment, ORR was 71 % (56 % CR+ Cru) and 67 % (60 % CR+ Cru) in arm A and B respectively. Five treatment-related deaths were reported, during induction chemotherapy in arm A (n = 2) and after IC+ HCT (n = 3). Median follow-up was 27.2 and 28.6 months in arm A and arm B respectively. Relapses occurred in 21 patients after the end of treatment (arm A: n = 16; Arm B: n = 5) with a median time to relapse of 15.1 and 8.5 months in arm A and B respectively. 2-y PFS in the experimental arm was 86.8% (95 CI, 76.6 to 98.3%). 2-y PFS in arm A will be given after the completion of the ongoing MRI review in this arm. The analysis of the prospective neuropsychological evaluations is pending. Conclusion:This study shows a favorable outcome of patients who received the IC+HCR arm. Improvement of the ORR after induction chemotherapy is still needed. The results of the 2-y PFS in arm A and of the neuropsychological evaluations are awaited to define the further standard of treatment in young patients with PCNSL. Fundings: French Government, Roche, Pierre Fabre Figure. Figure. Disclosures Choquet: Janssen: Consultancy; Celgene: Consultancy. Thyss:Takeda: Research Funding; Millennium: Research Funding. Soussain:Pharmacyclics: Research Funding; Roche: Research Funding; Celgene: Research Funding.

Background Lenalidomide, an immunomodulatory drug with antineoplastic and antiproliferative effects, showed activity in many single-group studies in relapsed or refractory mantle cell lymphoma. The aim of this randomised study was to examine the efficacy and safety of lenalidomide versus best investigator's choice of single-agent therapy in relapsed or refractory mantle cell lymphoma.Methods The MCL-002 (SPRINT) study was a randomised, phase 2 study of patients with mantle cell lymphoma aged 18 years or older at 67 clinics and academic centres in 12 countries who relapsed one to three times, had Eastern Cooperative Oncology Group performance status of 0-2, at least one measurable lesion to be eligible, and who were ineligible for intensive chemotherpy or stem-cell transplantation. Using a centralised interactive voice response system, we randomly assigned (2:1) patients in a permuted block size of six to receive lenalidomide (25 mg orally on days 1-21 every 28 days) until progressive disease or intolerability, or single-agent investigator's choice of either rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Randomisation was stratified by time from diagnosis, time from last anti-lymphoma therapy, and previous stem-cell transplantation. Individual treatment assignment between lenalidomide and investigator's choice was open label, but investigators had to register their choice of comparator drug before randomly assigning a patient. Patients who progressed on investigator's choice could cross over to lenalidomide treatment. We present the prespecified primary analysis results in the intention-to-treat population for the primary endpoint of progression-free survival, defined as the time from randomisation to progressive disease or death, whichever occurred first. Patient enrolment is complete, although treatment and collection of additional time-to-event data are ongoing. This study is registered with ClinicalTrials.gov, number NCT00875667.Findings Between April 30, 2009, and March 7, 2013, we enrolled 254 patients in the intention-to-treat population (170 [67%] were randomly assigned to receive lenalidomide, 84 [33%] to receive investigator's choice monotherapy). Patients had a median age of 68.5 years and received a median of two previous regimens. With a median follow-up of 15.9 months (IQR 7.6-31.7), lenalidomide signifi cantly improved progression-free survival compared with investigator's choice (median 8.7 months [95% CI 5.5-12.1] vs 5.2 months [95% CI 3.7-6.9]) with a hazard ratio of 0.61 (95% CI 0.44-0.84;p=0.004). In the 167 patients in the lenalidomide group and 83 patients in the investigator's choice group who received at least one dose of treatment the most common grade 3-4 adverse events included neutropenia (73 [44%] of 167 vs 28 [34%] of 83) without increased risk of infection, thrombocytopenia (30 [18%] vs 23 [28%]), leucopenia (13 [8%] vs nine [11%]), and anaemia (14 [8%] vs six [7%]).Interpretation Patients with relapsed or refractory mantle cell lymphoma ineligible for intensive chemotherapy or stem-cell transplantation have longer progression-free survival, with a manageable safety profi le when treated with lenalidomide compared with monotherapy investigator's choice options.

11013 Background: Since 2009 a network of 26 reference multidisciplinary centers aiming to improve the quality of care for sarcoma patients (pts) in France was granted by the French National Cancer Institute. We report here on the results of this network on patient management after 5 years. Methods: Data of the NetSarc network database include pts characteristics, previous treatment and diagnosis procedures, medical decision, survival and progression. From Jan 2010 to Dec 2014, 13454 newly diagnosed pts were included, soft tissue and visceral representing 10427 (77%) and 3027 (23%) respectively. These represent an estimated 78% of sarcoma case in France in 5 years. Individual Netsarc enters managed a median of 325 (range 39-1529) pts in 5 years. Results: 6955 women (52%) and 6499 men (48%), with a median age of 60y (range 0-101) were included. Soft tissue and visceral represented 10427 (77%) and 3027 (23%) pts respectively. LMS (12%), GIST (8.2%), DDLPS (7.3%) and UPS (11%) were the most frequent histotypes. 12% pts had metastases at diagnosis. Between 2010 and 2015, the proportion of pts reviewed in Netsarc reference centers prior to surgery increased from 41% to 48%. A higher number of pts managed in Netsarc centers had proper imaging of the primary tumor prior to surgery (86% vs 59%, p<0.0001), and had biopsy prior the first resection (80% vs 36%, p<0.0001). 10265 (76%) pts had a surgery, 4304 (42%) within the Netsarc network and 4639 (45%) outside the network, and unknown in 1322 (13%) pts). Patients whose primary surgery was performed in Netsarc centers had R0, R1, R2, and R (unknown or non evaluable) surgery in 49%, 27%, 7%, 16% vs 24%, 31%, 21%, 23% in centers outside Netsarc (p<0.000001). 865 (19%) pts had secondary resection after primary surgery in non NetSarc centers vs 252 (6%) in NetSARC centers (p<0.0001). Progression free survival (PFS) was better in patients managed in Netsarc reference centers (p=0.0008). Conclusions: Sarcoma pts managed in reference centers have a significantly higher rate of management according to CPGs, R0 surgery, less reoperations, and better PFS. The number of patients managed prior to surgery in reference centers increases slightly overtime.

This phase II study evaluated YM155, a novel small-molecule survivin suppressant, in combination with rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma (NHL) who failed or were not candidates for autologous stem cell transplant (ASCT). During 14-day cycles, 41 patients received YM155 (5mg/m(2)/d) by continuous intravenous (IV) infusion for 168 hours (day 1-7), and rituximab (375mg/m(2)) IV on days 1 and 8 during cycles 1-4 and repeated for 4 cycles every 10 cycles. Forty patients (97.6%) had prior rituximab and 15 patients (36.6%) prior ASCT. Most frequent grade 3-4 adverse events were neutropenia (19.5%) and thrombocytopenia (12.2%). In the per-protocol set (n=34), objective response rate was 50% and median progression-free survival 17.9 months. Median overall survival was not reached at study termination (median follow-up, 23 months). YM155 in combination with rituximab was tolerable with encouraging antitumor activity and durable responses in relapsed aggressive B-cell NHL patients.