scholarly journals EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i14-i14
Author(s):  
Timothy A. Ritzmann ◽  
Rebecca J Chapman ◽  
Donald Macarthur ◽  
Conor Mallucci ◽  
John-Paul Kilday ◽  
...  
Keyword(s):  
Management Strategy ◽  
Response Rate ◽  
Htert Expression ◽  
Intracranial Ependymoma ◽  
Long Term Follow Up ◽  
Post Hoc ◽  
1Q Gain ◽  
Final Cohort

Abstract Introduction Surgery and radiotherapy are established childhood ependymoma treatments. The efficacy of chemotherapy has been debated. We report final results of the SIOP Ependymoma I trial, with 12-year follow-up, in the context of a post-hoc analysis of more recently described biomarkers. Aims and Methods The trial assessed event free (EFS) and overall survival (OS) of patients aged three to 21 years with non-metastatic intracranial ependymoma, treated with a staged management strategy targeting maximum local control. The study also assessed: the response rate (RR) of subtotally resected (STR) disease to vincristine, etoposide and cyclophosphamide (VEC); and surgical operability. Children with gross total resection (GTR) received radiotherapy of 54 Gy in 30 daily fractions over six weeks, whilst those with STR received VEC before radiotherapy. We retrospectively assessed methylation and 1q status alongside hTERT, RELA, Tenascin C, H3K27me3 and pAKT expression. Results Between 1999 and 2007, 89 participants were enrolled, 15 were excluded with metastatic (n=4) or non-ependymoma tumours (n=11) leaving a final cohort of 74. Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. 1q gain was associated with poorer EFS (p=0.002, HR=3.00, 95%CI 1.49–6.10). hTERT expression was associated with worse five-year EFS (20.0% Vs 83.3%, p=0.014, HR=5.8). GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.006, HR=2.81, 95% confidence interval 1.35–5.84). There was an improvement in GTR rates in the latter half of the trial (1999-2002 32.4% versus 2003-2007 56.8%). Despite the protocol, 12 participants with STR did not receive chemotherapy. However, chemotherapy RR was 65.5% (19/29, 95%CI 45.7–82.1). Conclusions VEC exceeded the pre-specified RR of 45% in children over three years with STR intracranial ependymoma. However, cases of inaccurate stratification at treating centres highlights the need for rapid central review. We also confirmed associations between 1q gain, hTERT expression and outcome.

scholarly journals SIOP Ependymoma I: Final results, long term follow-up and molecular analysis of the trial cohort: A BIOMECA Consortium Study

2021 ◽  
Author(s):  
Timothy A Ritzmann ◽  
Rebecca J Chapman ◽  
John-Paul Kilday ◽  
Nicola Thorp ◽  
Piergiorgio Modena ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Randomised Trial ◽  
Protocol Violation ◽  
Long Term Follow Up ◽  
Grade 3 ◽  
Post Hoc ◽  
Chemotherapy Efficacy ◽  
1Q Gain

Background: SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) from non-metastatic intracranial ependymoma in children aged 3 to 21 years, treated with a staged management strategy. Chemotherapy efficacy in ependymoma is debated and therefore the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide and cyclophosphamide (VEC) was an additional primary outcome. We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers. Methods: 74 participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation and 1q status were evaluated, alongside hTERT, ReLA, Tenascin-C, H3K27me3 and pAKT expression. Results: Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.003, HR=2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (p=0.005, HR=2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (p=0.003, HR=2.70, 95%CI 1.49-6.10 and p=0.014, HR=5.8, 95%CI 1.2-28 respectively) and H3K27me3 loss with worse OS (p=0.003, HR=4.6, 95%CI 1.5-13.2). DNA methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding a prespecified 45% RR. Conclusions: RR of STR to VEC exceeded the pre-specified criterion for efficacy. However, cases of inaccurate treatment stratification highlighted the need for rapid central review. Prognostic associations for 1q gain, H3K27me3 and hTERT were confirmed.

scholarly journals Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis

2021 ◽  
pp. 135245852110002
Author(s):  
Bruce AC Cree ◽  
Jeffrey A Cohen ◽  
Anthony T Reder ◽  
Davorka Tomic ◽  
Diego Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Therapeutic Benefit ◽  
Disease Modifying Therapies ◽  
Long Term Follow Up ◽  
Post Hoc ◽  
Switch Group ◽  
Relevant Outcome

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI). Objective and Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5–1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo. Results: At 8 years’ follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%–43.1%) of assessed participants in the IFNβ-1a–fingolimod switch group and 41.9% (36.6%–47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a–fingolimod switch group than on continuous fingolimod (5.4% [3.0%–9.5%] vs 14.2% [10.8%–18.4%], p = 0.01). Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.

School-Age Outcome of Fetuses with Isolated Complete Septum Pellucidum Agenesis at Prenatal Magnetic Resonance Imaging

2021 ◽  
Author(s):  
Andrea Righini ◽  
Giana Izzo ◽  
Chiara Doneda ◽  
Barbara Scelsa ◽  
Cecilia Parazzini
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Septum Pellucidum ◽  
School Age ◽  
Resonance Imaging ◽  
Long Term Follow Up ◽  
Prenatal Magnetic Resonance Imaging ◽  
Final Cohort

Abstract Objective To the best of our knowledge, there have not been studies to address the issue of long-term follow-up of patients with prenatal diagnosis of isolated complete septum pellucidum agenesis (SPA). The aim of this study was to acquire information about the school-age outcome of such patients as a resource for counseling parents receiving this prenatal finding. Methods From a large fetal magnetic resonance (MR) database, we selected only those cases with isolated complete SPA as confirmed by two senior pediatric neuroradiologists in consensus; we then gathered information from the parents of those children who had reached the school age. Results None among the 12 cases (mean age at follow-up: 8.7 years, range: 6–13 year) of the resulting final cohort presented visual or stature deficits; only one required special teaching assistance in school. All other 11 children resulted without any notable academic issue. Conclusion Our report may provide information of practical value about the school-age outcome of fetuses detected by prenatal MR imaging to carry isolated complete SPA.

Durability of complete response (CR) with atezolizumab (atezo) in locally advanced/metastatic urothelial carcinoma (mUC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4527-4527
Author(s):  
Yohann Loriot ◽  
Arjun Vasant Balar ◽  
Robert Dreicer ◽  
Jean H. Hoffman-Censits ◽  
Jose Luis Perez-Gracia ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Complete Response ◽  
First Response ◽  
Long Term Follow Up ◽  
Metastatic Urothelial Carcinoma ◽  
Post Hoc ◽  
Clinical Trial Information ◽  
Disposition Time

4527 Background: Atezo (anti–PD-L1) has been shown to elicit CRs in a number of mUC patients (pts) in clinical trials. We sought to describe the kinetics, durability and outcomes associated with these CRs in Ph I (PCD) and II (IMvigor210) atezo studies, each with long-term follow-up. Methods: In PCD (pre-treated mUC) and IMvigor210 (Cohort 1, cisplatin-ineligible untreated mUC; Cohort 2, platinum-treated mUC), pts received atezo per protocol (Petrylak JAMA Oncol 2018; Balar Lancet 2017; Rosenberg Lancet 2016). This post hoc analysis descriptively assessed pt disposition, time to and duration of RECIST 1.1 response and overall survival in pts with CR. Results: CR rates were 13%, 8% and 7% in PCD, IMvigor210 Cohort 1 and Cohort 2, respectively. First response was PR in most pts with CR. Median CR duration was > 3 y in PCD, not estimable (NE) in IMvigor210 Cohort 1 and > 2 y in Cohort 2 (Table). At data cutoff, all but 2, 0 and 1 pts were alive, respectively; across studies, ≥ 40% of pts with CR were on treatment. CR pts had a first response (PR/CR) by a median of 3.5 cycles. Further pt characteristics and survival outcomes will be reported. Conclusions: Across Ph I/II atezo mUC studies, CRs appeared durable (median duration > 2 y) despite small pt numbers. Most pts with CR were alive, with responses ongoing after long-term follow-up (median follow-up > 30 mo). Clinical trial information: NCT01375842, NCT02951767, NCT02108652. [Table: see text]

Active Immunotherapy with FavId® (Id/KLH) Following Rituximab Induction: Long-Term Follow-Up of Response Rate Improvement (RRI) and Disease Progression in Follicular Lymphoma Patients (pts).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 691-691 ◽  
Author(s):  
Omer N. Koc ◽  
Charles Redfern ◽  
Peter H. Wiernik ◽  
Fred Rosenfelt ◽  
Jane N. Winter ◽  
...  
Keyword(s):  
Disease Progression ◽  
Median Time ◽  
Response Rate ◽  
Published Data ◽  
Late Response ◽  
Gm Csf ◽  
Best Response ◽  
Long Term Follow Up

Abstract Background: Studies of Id/KLH immunotherapy in treatment naïve (TN) fNHL pts following first remission from chemotherapy have demonstrated a prolonged duration of remission. We expanded this approach in a PhII trial to include TN and relapsed/refractory (R/R) pts with stable disease (SD) or PR or CR/CRu following 4 wkly doses of rituximab. We report here long term follow up of RRI, defined as the % of pts who converted from SD to PR or PR to CR/CRu following initiation of Id/KLH treatment, and analysis of disease progression. Treatment: Pts received rituximab (375mg/m2 i.v. wkly x 4 during wk1–4) and those with stable or responsive disease received Id/KLH (1 mg s.q. mo x 6) starting on wk 12 along with GM-CSF (250 mcg, s.q.) on days 1–4. Pts continued to receive booster injections on a reduced schedule until disease progression. Radiological scans, performed every 3 mos, were reviewed centrally. Disease progression and response were assessed using modified Cheson criteria. This data analysis was performed 32 mo from end of enrollment. Results: 103 pts were enrolled and received rituximab; 89 pts had ≥SD and received Id/KLH + GM-CSF of whom, 54 were R/R, and 35 were TN. The overall response rate (ORR) was 47% (42/89) at mo 3. After the initiation of Id/KLH dosing, ORR improved to 63% (56/89). In RRI pts, median time to best response was 9.1 mos from start of rituximab treatment (5.2 – 29.6 mos). 12 of 39 PR pts (31%) converted to CR/Cru. 14 of 43 SD pts (33%) converted to PR. Pt Groups # of Pts % Prog Free Median TTP Est by K-M (mo) Pts w/RRI 26 69% 37.9 TN rituximab responders 23 70% Not Reached (NR) Rituximab responders (All) 42 60% NR Non Responders (All) 47 36% 14.9 All Pts 89 47% 18.2 TN Pts (All) 35 66% NR Relapsed Pts (All) 54 37% 16.8 Conclusion: RRI following FavId is seen in nearly one third of pts. The magnitude of this improvement, the number of conversions to CR/CRu and median time to best response (9 mo and as late as 29.6 mo) suggests this is likely to be a FavId effect rather than late response to rituximab. Responders and TN pts show more durable responses compared to previously published data for rituximab therapy. FavId may also confer a benefit for nonresponders and R/R pts relative to rituximab alone. To confirm benefit of FavId following rituximab induction, a placebo controlled PhIII study was initiated; it completed enrollment in Jan 06. RRI data from this study is expected to be available in Nov 06.

Long Term Follow up of Patients with Immune Thrombocytopenia Receiving Rituximab

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4675-4675 ◽  
Author(s):  
Khalid Al-Habsi ◽  
Murtadha K. Al-Khabori ◽  
Muhanna Al-Muslahi ◽  
Anil Pathare ◽  
Khalil Al Farsi ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Median Time ◽  
Immune Thrombocytopenia ◽  
Response Rate ◽  
Age At Diagnosis ◽  
Second Line ◽  
Long Term Follow Up ◽  
Chronic Immune Thrombocytopenia

Abstract Abstract 4675 Introduction: Rituximab has been used in the management of chronic immune thrombocytopenia (ITP) with promising results. The risk of losing response, however, is yet to be determined with long term follow up. Method: We retrospectively analyzed 32 consecutive patients (20 females, 12 males) with ITP (including 6 patients with secondary ITP) treated with rituximab in two tertiary care hospitals in Oman between May 2006 and May 2011. Response criteria were based on the International Consensus report (Rodeghiero F et al. Blood 2009). Result: The median age at diagnosis was 25 years (range, 4 – 58). Clinical presentation ranged from mild echymosis to more severe central nervous system bleeding. Patients received a median of one line of therapy before rituximab (range, 1–4), including 3 patients who failed splenectomy. Patients received intravenous rituximab using 375 mg/m2 once weekly for 4 weeks. The median time from diagnosis to receiving rituximab was 21 months (range, 1– 177). Only one patient was positive for Hepatitis C virus, but no hepatitis B or HIV positive in this cohort. Anti nuclear antibody was positive in 34% (10/29) of patients. The median hemoglobin and platelet counts at diagnosis were 12 g/dl (range, 5–16) and 11×109/L (range, 1–60) respectively. The median follow up time after rituximab was 26 months (95% confidence interval: 11–40). The overall cumulative response rate was 59% (partial response of 15% and complete response of 44%). The median time to respond was 30 days (Standard error [SE] 49) with a response rate of 44% at 4 weeks (95% Confidence interval: 29–62%). The multivariable Cox model analysis (variables include: age at diagnosis, gender, number of previous therapies and primary vs. secondary) revealed none of the variables included to be statistically significant. The cumulative rate of loss of response was 32% (6/19) with a median time to lose response of 54 months (SE, 0.03). In patients who lost response, the median time to lose response was 17 months (SE, 14). Of the 6 patients who lost response, 4 received a second course of rituximab and all 4 achieved a full response. No major side effects to rituximab were reported during the follow up. Conclusion: Rituximab is an effective and a well tolerated second line therapy for ITP. The response to rituximab can be maintained for a long duration with a high rate of response after retreatment. None of the pretreatment variables studied carried a significant predictive value for response. The study was limited by the small sample size and further larger prospective studies are recommended. Disclosures: Off Label Use: Rituximab was used in our study as a second line for the management of chronic immune thrombocytopenia.

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