scholarly journals ACTR-38. A SINGLE CENTER STUDY: LONG-TERM OUTCOMES OF COMBINED CHEMORADIATION THERAPY WITH TEMOZOLOMIDE FOR NEWLY DIAGNOSED GLIOBLASTOMA IN KOREAN PATIENT

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi21-vi21
Author(s):  
Kyeong-O Go ◽  
Ha Young Yang ◽  
Kihwan Hwang ◽  
Jung Ho Han ◽  
Hyoung Soo Choi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Adjuvant Treatment ◽  
Genetic Factors ◽  
Newly Diagnosed ◽  
Factors Affecting ◽  
Korean Patients ◽  
Significant Difference ◽  
Newly Diagnosed Glioblastoma

Abstract In newly diagnosed glioblastoma (GBM), Temozolomide (TMZ) during and after radiation therapy has become standard treatment. This study describes the long-term use and follow-up results of this therapy for GBM. From 2004 to 2013 in a single institute, 112 Korean patients with newly diagnosed GBM were analyzed retrospectively. The Kaplan-Meier method, the two-sided log-rank test and Cox’s regression analysis was used to determine survival and its affecting factors. The toxicities of TMZ were evaluated using CTCAE v5.0. During the median follow-up period of 18.8 months, median PFS and OS were 9.2 and 20.3 months, respectively. This better survival outcome than the Stupp’s original study might be probably a large treatment effect of a single institution, ethnicity, and associated genetic factors. The TMZ during radiation therapy was completed in 108 patients (96.4%) and TMZ after radiation therapy in 59 patients (52.7%). Eight patients presented with grade 3 or 4 hematologic toxic effects during the protocol. Sixty-six patients (58.9%) received salvage treatment because of the poor response to adjuvant treatment or progression of the disease who achieved completion of adjuvant treatment was shown significantly longer median OS (p= 0.007) and PFS (p< 0.001). Age (< 60 years), preoperative KPS score (≥ 90), the extent of resection (≥ 78% by volumetric measurement, gross total resection), and completion of the Stupp’s protocol were significant factors affecting better survival. Between the sexes, and ages over 65 years did not show any significant difference among their groups. With marginal significances, the mutated IDH-1 and the methylated MGMT promoter showed longer median PFS(p= 0.075 and 0.777, respectively) and OS (p= 0.085 and 0.131, respectively). TMZ during and after radiation therapy might be effective and safe for newly diagnosed Korean patients with GBM. Further studies about various clinical and genetic factors affecting better survival are mandatory.

Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial.

1993 ◽  
Vol 11 (8) ◽  
pp. 1523-1528 ◽  
Author(s):  
F B Stehman ◽  
B N Bundy ◽  
G Thomas ◽  
H M Keys ◽  
G d'Ablaing ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Locally Advanced ◽  
Hypoxic Cell ◽  
Gynecologic Oncology Group ◽  
Advanced Carcinoma ◽  
Free Interval ◽  
Significant Difference ◽  
Long Term Follow Up

PURPOSE Long-term follow-up data of a randomized trial that compared hydroxyurea and the hypoxic-cell radiosensitizer to misonidazole as adjuncts to standard radiation therapy in locally advanced carcinoma of the cervix are reported. PATIENTS AND METHODS Three hundred eight women were entered, and all 294 eligible patients are assessable as randomized. Eighty-one percent of patients have been monitored for 5 years or to death. RESULTS There was an advantage for hydroxyurea in progression-free interval and survival (P = .05 and P = .066, respectively). There was no significant difference in the distribution of sites of failure between the regimens. For the 39% of patients with stages III to IVA disease, the advantage in progression-free interval for hydroxyurea was significant (47.8% v 33.6%). More leukopenia occurred on the hydroxyurea regimen than on the misonidazole regimen. CONCLUSION In summary, these data provide stronger evidence than our previous analysis that hydroxyurea is superior to misonidazole as an adjunct to radiation therapy. For patients with locally advanced carcinoma of the cervix, hydroxyurea continues to be the adjunct of choice with radiation.

scholarly journals Serial FLT PET imaging to discriminate between true progression and pseudoprogression in patients with newly diagnosed glioblastoma: a long-term follow-up study

2018 ◽  
Vol 45 (13) ◽  
pp. 2404-2412 ◽  
Author(s):  
Cyrillo G. Brahm ◽  
Martha W. den Hollander ◽  
Roelien H. Enting ◽  
Jan Cees de Groot ◽  
A. Millad Solouki ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Newly Diagnosed ◽  
Follow Up Study ◽  
Flt Pet ◽  
Long Term Follow Up ◽  
Newly Diagnosed Glioblastoma ◽  
True Progression

scholarly journals Long Term Follow up from the NCRI AML17 Trial of Attenuated Arsenic Trioxide and ATRA Therapy for Newly Diagnosed and Relapsed Acute Promyelocytic Leukaemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 897-897
Author(s):  
Nigel H Russell ◽  
Alan K. Burnett ◽  
Robert K Hills ◽  
Sophie Betteridge ◽  
Michael Dennis ◽  
...  
Keyword(s):  
High Risk ◽  
Low Risk ◽  
Newly Diagnosed ◽  
Molecular Monitoring ◽  
Term Survival ◽  
Cns Disease ◽  
Significant Difference ◽  
Risk Of Relapse

Abstract Background: Two randomized studies have reported comparison of the "chemo-free" combination of ATO+ATRA with Anthracycline/ ATRA (AIDA) in APL. The GIMEMA-AMLSG-SAL trial, using a daily schedule improved both survival and relapse risk in patients with newly diagnosed, low or intermediate-risk APL. (Lo Coco et al., NEJM 2013; 369: 111-21). The NCRI AML17 trial using an attenuated dosing schedule in all risk groups resulted in a very low risk of relapse, significantly better EFS but no significant survival advantage Aims: The NCRI AML17 Trial compared AIDA vs the chemo-free combination of ATO (in an attenuated schedule) + ATRA. Here we present long term survival results for randomized patients and for 24 patients who received the same chemo-free schedule of ATO + ATRA after relapsing from the AIDA arm of the trial. Methods: From May 2009 to October 2013, 235 patients aged >16 who entered the AML17 trial with molecularly confirmed APL were randomized to either ATRA+ATO (8 week induction 0.3mg/kg d1-5 w1, 0.25mg/kgx2/w w2-8, followed by 4 consolidation courses of 0.3mg/kgx2 w1, 0.25mg/kgx2/ w2-4 (63 ATO doses) OR AIDA schedule: Idarubicin (Ida)12mg/m2 d2,4,6,8 + ATRA to d60) (induction) then Ida 5mg/m2 d1-4 + ATRA d1-15 (Course 2); Mitox. 10mg/m2 d1-4 + ATRA d1-15 (course 3); Ida 12mg/m2 d1 + ATRA d1-15 (Course 4). ATRA was 45mg/m2/d. Maintenance was not given. High risk patients could receive Gemtuzumab Ozogamicin (d1,6mg/m2). Another 70 patients were treated in AML17 with AIDA after closure of the randomization. 25/189 patients relapsed post AIDA and 24 were treated with a median of 4 cycles (range 1-5) of ATRA + ATO, 11/24 were later transplanted. Follow-up is complete to 1 January 2016. Results: The median age was 47y (16-77); 57 had WBC>10x109/L (27 AIDA, 30 ATRA+ATO) and 49 (24 AIDA, 25 ATRA+ATO) were >60y. The early results of the randomization for newly diagnosed patients have been reported (Burnett et al. Lancet Oncol. 2015, 16 (13):1295). 91% entered morphological CR with no significant difference in CR rate between the arms (Chemo-free 94%, Chemo 89%; OR 0.54 (0.21-1.34), p= 0.18). The OS at 4 years was 93% (Chemo-free) vs 89% (Chemo), HR 0.60 (0.26-1.42) p= 0.2, but EFS was significantly superior with ATRA+ATO (91% vs 70%, HR 0.35 (0.18-0.68) p=0.002). With a longer median follow-up of 53.4 months 5-year survival is now 93% (chemo-free) v 87% (chemo) (HR 0.61 (0.27-1.35) p=0.2). A significant reduction in relapse (2% vs 16% at 5 years, HR 0.19 (0.09-0.45) p=0.0005) translates to continuing significant RFS benefit for the chemo-free approach (96% vs 82%; HR 0.30 (0.13-0.67) p=0.004). This is seen both in low risk (95% vs 86% HR 0.45 (0.17-1.20) p=0.11) and high risk disease (100% vs 69% HR 0.10 (0.02-0.46) p=0.003), p=0.11 for heterogeneity. 25 patients relapsed following AIDA therapy, of whom 1 died in frank relapse before treatment could be initiated and 24 (5 with concomitant CNS involvement) were treated with the attenuated ATO + ATRA schedule. Of these 16 were treated at molecular relapse, reflecting the value of centralised MRD monitoring as part of the trial protocol. All 24 patients achieved molecular CR post ATO +ATRA. Eleven patients were transplanted (8 autograft, 3 allograft) including 4 of the 5 patients with CNS disease. 3 patients have had a second molecular relapse after ATO + ATRA salvage (1 transplanted and 2 not transplanted). The 3-year overall survival post-relapse is 96% with the only other death occurring post-transplant after 37 months. Summary/Conclusion: The combination of ATO + ATRA continues to show a very low risk of relapse irrespective of risk group resulting in significantly better RFS compared to AIDA and excellent survival but no survival benefit has emerged primarily because of effective salvage interventions for AIDA-treated patients with most patients treated at molecular relapse. Molecular monitoring for t(15;17) is therefore essential to optimize therapy with AIDA. For patients treated with frontline ATO+ATRA molecular monitoring is of questionable value once achievement of molecular CR has been documented, but molecular surveillance remains important in those with relapsed disease. The attenuated AML17 ATO dosing approach is effective both upfront and in patients relapsing post AIDA and these results question the role of transplantation as consolidation in patients achieving molecular CR2 with ATO + ATRA who do not have CNS disease at relapse. Disclosures Burnett: CTI Life Sciences, London: Employment. Hills:TEVA: Honoraria. Grimwade:TEVA: Research Funding.

Long-Term Effects on Volume Change in Musculocutaneous Flaps after Head and Neck Reconstruction

2018 ◽  
Vol 35 (04) ◽  
pp. 235-243 ◽  
Author(s):  
Akiko Sakakibara ◽  
Junya Kusumoto ◽  
Shunsuke Sakakibara ◽  
Takumi Hasegawa ◽  
Masaya Akashi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Head And Neck ◽  
Muscle Volume ◽  
Musculocutaneous Flap ◽  
Flap Reconstruction ◽  
Musculocutaneous Flaps ◽  
Significant Difference ◽  
Long Term Follow Up

Objective Musculocutaneous flap reconstruction surgery is one of the standard procedures following head and neck cancer resection. However, no previous studies have classified flaps in terms of muscle and fat or examined them after long-term follow-up. The purpose of this study was to estimate the fat and muscle volume changes in musculocutaneous flaps during long-term follow-up. Methods We conducted a retrospective analysis of 35 patients after musculocutaneous flap reconstruction. The total, fat, and muscle volumes of the musculocutaneous flaps were measured using 3-dimensional images. Changes in flap volumes over time (1 month, 1 year [POY1], and 5 years [POY5] postoperatively) were assessed. Flap persistence was calculated using flap volumes at 1 month after reconstruction for reference. Results Flap persistence at POY5 was 42.0% in total, 64.1% in fat, and 25.4% in muscle. Muscle persistence was significantly decreased (p < 0.0001). In a multiple regression analysis, decreased body mass index (BMI) of ≥ 5% influenced fat persistence less than muscle persistence at POY1; however, there was no significant difference at POY5. Postoperative radiation therapy was associated with a significant decrease in total flap persistence at POY1 (p = 0.046) and POY5 (p = 0.0097). Muscle persistence significantly decreased at POY5 (p = 0.0108). Age significantly influenced muscle volume at POY1 (p = 0.0072). Conclusion Reconstruction flaps are well-preserved with high fat-to-muscle ratios. Recommendations for weight maintenance are necessary for patients less than 2 years after surgery due to the influence of BMI on fat persistence. Radiation therapy is necessary for some patients based on their disease state. Intensity-modulated radiation therapy can be offered to reduce scattering irradiation to normal tissues.

Long Term Follow-Up Shows No Clinical Benefit for CD34+ Selection of Autologous Transplants Following Myeloablative Therapy in Patients with Newly Diagnosed Myeloma : An EBMT Phase III Randomized Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 921-921 ◽  
Author(s):  
Jean-Henri Bourhis ◽  
Yasmina Bouko ◽  
Serge Koscielny ◽  
Hildegard Greinix ◽  
Gunter Derigs ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Median Time ◽  
Clinical Benefit ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Cd34 Selection ◽  
Selection Of

Abstract CD34+ selection of peripheral blood progenitor cells (PBPC) was used in Multiple Myeloma (MM) in an attempt to reduce tumor cell contamination and relapse rate. From May 1995 to November 1999, 127 patients from 17 EBMT centers with newly diagnosed advanced MM were entered into a phase III trial. Responders to 3 cycles of VAD were randomized to receive either CD34+ selected (arm A) or unselected PBPC (arm B) following myeloablative conditioning treatment. PBPC were harvested following mobilization with cyclophosphamide 4g/m² and G-CSF (Filgrastim, AMGEN, Europe). Conditioning regimen in both arms was TBI and high dose melphalan 140 mg/m². CD34+ cell selection was performed in arm A using the CellPro Ceprate-SC device. The analysis concerns the 111 patients who were transplanted (56 arm A and 55 arm B). The median follow-up at the time of the analysis was 65 months. CD34+ selection resulted in a median purity of 87% and a yield of 50%. Molecular analysis showed a median tumor cell depletion of 2.0 log (range 0.3–85.5). The median number of CD34+ cells reinfused/kg was 5.8 x 106 (1.42–50.4) in arm A and 7.4x106 (1.85–99.2) in arm B. The median time to neutrophil engraftment (ANC >0.5x109/l) was 10 days (range 8–14) in arm A and 10 days (range 8–21) in arm B. The median time to platelet engraftment (plts>20 x 109/l) was 11 days (range 5–26) in arm A and 9 days (range 5–42) in arm B (p=0.005). One patient died before platelets engraftment in arm A. Twelve patients experienced at least one episode of serious infection (total episodes =17) before day 100 in arm A compared to 3 patients (total episodes = 6) in arm B (p=0.02). For 3 patients in arm A, these infections were fatal (including the patient who died before time to platelet engraftment). There was no significant difference in CR rate at 1 year as defined by EBMT/IBMTR/ABMTR criteria (27% in arm A and 20% in arm B). The 5 year overall survival (OS) was 51% in arm A and 45% in arm B (p=0.80). The 5 year event free survival was 20% in arm A and 18% in arm B (p=0.45). The increased incidence of severe infections in the CD34+ selected arm in the early post transplant may be due to impaired immune reconstitution. Thus, no long term clinical benefit is obtained by CD34+ selection despite significant tumor cell reduction.

Long-term follow-up after BCNU wafer implantation in patients with newly diagnosed glioblastoma

2021 ◽  
Vol 86 ◽  
pp. 202-210
Author(s):  
Ichiyo Shibahara ◽  
Kazuhiro Miyasaka ◽  
Akane Sekiguchi ◽  
Hiromichi Ishiyama ◽  
Madoka Inukai ◽  
...  
Keyword(s):  
Newly Diagnosed ◽  
Bcnu Wafer ◽  
Long Term Follow Up ◽  
Newly Diagnosed Glioblastoma

A TITE-CRM phase I/II study of disulfiram and copper with concurrent radiation therapy and temozolomide for newly diagnosed glioblastoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2033-2033 ◽  
Author(s):  
Jiayi Huang ◽  
Todd DeWees ◽  
Jian Li Campian ◽  
Milan G Chheda ◽  
George Ansstas ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Newly Diagnosed ◽  
Elevated Liver Enzymes ◽  
Significant Difference ◽  
Newly Diagnosed Glioblastoma ◽  
Recommended Phase Ii Dose

2033 Background: Disulfiram (DSF) has shown promising activity against glioblastoma in preclinical studies and is more effective when combined with copper (Cu). Our previous phase I study established the maximum tolerated dose (MTD) of DSF when combined with adjuvant temozolomide (TMZ). This phase I/II study aims to establish the MTD when disulfiram and copper are combined with concurrent radiation therapy (RT) and TMZ for newly diagnosed glioblastoma and to explore preliminary efficacy. Methods: Eligible patients were treated with standard RT and TMZ plus escalating doses of DSF (250 mg - 375 mg PO QD) and Cu (2 mg PO TID), followed by adjuvant TMZ plus DSF (500 mg/day) and Cu. The time-to-event continual reassessment method (TITE-CRM) was used to continuously estimate the probability of dose-limiting toxicity (DLT) and to assign patients to doses with an estimated DLT probability of approximately 20% with a margin of 5%. Tumor mutations were evaluated with next-generation sequencing for all patients. Results: Eighteen glioblastoma patients were treated with the study therapy: 8 with DSF of 250 mg/day and 10 with 375 mg/day. Three DLTs were observed: 1 with 250 mg/day (grade 2 urinary incontinence and ataxia), and 2 with 375 mg/day (both grade 3 elevated liver enzymes). DSF had an estimated DLT probability of 10% (95% CI: 3-29%) at 250 mg/day, and 21% (95% CI: 7-42%) at 375 mg/day. After a median follow-up of 12.3 months, 1-year progression-free survival (PFS) was 57%, and 1-year overall survival (OS) was 69%. There was no significant difference in PFS/OS when stratified by DSF doses, surgical extent, or MGMT methylation status. However, glioblastomas with IDH1 (n = 6), BRAF (n = 2), or NF1 (n = 1) mutations had significantly better PFS and OS than those without the mutations: 1-year PFS: 100% vs 22%, respectively, p = 0.001; 1-year OS: 100% vs 42%, respectively, p = 0.006. Conclusions: The MTD of DSF with RT/TMZ/Cu for glioblastoma is 375 mg/day, and the recommended phase II dose is 250 mg/day. Although confirmation with larger sample size is needed, the combination demonstrates promising preliminary efficacy for the subset of glioblastoma with IDH1, BRAF, and NF1 mutations. Clinical trial information: NCT02715609.

scholarly journals CTNI-74. PHASE 3 TRIDENT TRIAL: CONCOMITANT RADIATION THERAPY (RT) AND TEMOZOLOMIDE +/- TUMOR TREATING FIELDS (TTFIELDS) IN NEWLY DIAGNOSED GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii59-ii60
Author(s):  
Wenyin Shi ◽  
Lawrence Kleinberg ◽  
Suriya A Jeyapalan ◽  
Samuel Goldlust ◽  
Seema Nagpal ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Free Survival ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard-of-care for newly diagnosed glioblastoma (ndGBM). In the EF-14 Phase 3 trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased survival of ndGBM patients without increasing systemic toxicity. TTFields-related AEs were mainly skin AEs. In preclinical models, TTFields increase the therapeutic effects of radiation therapy (RT). A pilot study showed that TTFields concomitant with RT and TMZ is well tolerated. The benefit of concomitant TTFields with RT and TMZ will be tested in the TRIDENT trial. METHODS TRIDENT is an international phase III randomized trial comparing standard RT with TMZ vs the triple combination of RT/TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields/TMZ. TTFields (200 KHz) will be delivered &gt;18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed ndGBM, ≥ 18 years, KPS ≥ 70, either sex, post-surgery or biopsy, and amenable for RT/TMZ therapy will be stratified by extent of resection and MGMT promoter methylation status. The primary endpoint is overall survival (OS). Secondary end points: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS6M, PF12M, PFS2Y); severity and frequency of AEs (CTCAE V5.0); pathological changes in resected GBM tumors post treatment; quality of life (EORTC QLQ-C30); and correlation of OS to TTFields compliance. The hypothesis is that concomitant TTFields/RT/TMZ will significantly improve OS versus RT/TMZ. Sample size (N=950; 475/arm) will detect a HR&lt; 0.8 with 5% type I error. Survival will be measured from the time of randomization until date of death. At the time of analysis, patients lost to follow-up or still on protocol follow-up will be censored at the last date known to be alive.

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