scholarly journals ATIM-46. A MULTICENTER, PHASE I, TRIAL OF RADIATION, TEMOZOLOMIDE AND RRx-001 FOLLOWED BY MAINTENANCE TEMOZOLOMIDE WITH OR WITHOUT RRx-001 IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi11-vi12
Author(s):  
Robert Aiken ◽  
Howard Fine ◽  
Nicholas Butowski
Keyword(s):  
Overall Survival ◽  
Confidence Interval ◽  
Survival Time ◽  
Median Time ◽  
Lower Limit ◽  
Dose Range ◽  
Newly Diagnosed ◽  
Overall Survival Time ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND RRx-001 is an aerospace-derived radiochemosensitizer with minimal toxicity. The purpose of this trial was to establish the safety of RRx-001 plus radiotherapy and temozolomide and to look for signals of enhanced anti-tumor activity in patients with newly diagnosed glioblastoma. METHODS In this non-randomized trial called G-FORCE-1 (NCT02871843), 18 newly diagnosed, histologically verified glioblastoma patients were enrolled. The treatment plan included 6 weeks of temozolomide and radiotherapy with RRx-001 followed by maintenance temozolomide with or without RRx-001. Four cohorts of 3 patients received intravenous RRx-001 at doses of 0.5,1,2, or 4 mg/week during radiotherapy only. An additional two cohorts of 3 patients received 4 mg/week of RRx-001 during radiotherapy and 0.5 mg/week of RRx-001 during temozolomide maintenance. RESULTS There were no grade 3 or 4 dose-limiting toxicity events (DLT) that appeared related to RRx-001 for the dose range of 0.5 to 4 mg/week. A maximum tolerated dose was not defined. The main adverse event related to RRx-001 was injection-site reaction. The overall response rate was 16.7% (3 PR out of 18) pending confirmation since pseudoprogression was prevalent, and the disease control rate was 61.1% (3 PR, 8 SD out of 18). The median time to tumor progression (95% confidence interval lower limit of 9.2 months to NR) and the median overall survival time (95% confidence interval lower limit of 12.9 months to NR) have not been reached after a median follow-up time of 10.3 months (range: 2.7 to 25 months.). CONCLUSION RRx-001 was well tolerated with concurrent temozolomide and radiotherapy and with temozolomide maintenance in 18 newly diagnosed glioblastoma patients. The primary objective to determine the MTD of RRx-001 was not met, since no DLTs occurred. The median time to progression and overall survival time have not been met after a median follow up time of 10.3 months.

scholarly journals ATIM-35. THE ASSOCIATIONS BETWEEN TOTAL LYMPHOCYTE COUNTS AFTER CONCOMITANT CHEMORADIATION WITH OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi9-vi9
Author(s):  
Stephen Ahn ◽  
Jae-Sung Park ◽  
Yong Kil Hong ◽  
Seung Ho Yang ◽  
Sin-Soo Jeun
Keyword(s):  
Overall Survival ◽  
Complete Blood Count ◽  
Malignant Tumors ◽  
P Value ◽  
Newly Diagnosed ◽  
Total Lymphocyte ◽  
Concomitant Chemoradiation ◽  
Newly Diagnosed Glioblastoma ◽  
The Relationship

Abstract Several studies have been conducted to determine the relationship between post-treatment total lymphocyte count (TLC) and overall survival (OS) in patients with malignant tumors including glioblastomas (GBMs). In this retrospective study, whether patients with newly diagnosed GBM experience significant lymphopenia after concomitant chemoradiation (CCRT) was evaluated, and whether TLC after this treatment is associated with OS in the treated population was examined. Using electronic medical records, all patients newly diagnosed with GBM between 2008 and 2016 at Seoul St. Mary’s Hospital were retrospectively examined. The eligible criteria included the following: 1) craniotomy with surgical resection or biopsy, 2) completion of CCRT, 3) accessible baseline and/or follow-up complete blood count (CBC). Median TLC significantly decreased after completion of CCRT, compared to TLC at baseline (1,742 versus 1,319 cells/mm3, P-value < 0.001). Patients with TLC < 1,200 cells/mm3 at 4 weeks after the completion of CCRT showed shorter survival than those with TLC ≥ 1,200 cells/mm3 with median OS of 14.5 versus 21.0 months (P-value = 0.017). Also, in multivariate analysis for OS, TLC < 1,200 cells/mm3 at 4 weeks after the completion of CCRT (HR 1.97, 95% CI 1.61 – 2.25, P-value = 0.004) were significantly associated with shorter survival. The results from the present study indicate that treatment-related total lymphocyte counts after CCRT is associated with worse survival in patients with newly diagnosed GBM.

Second-Line Treatment with Imatinib (IM) after Crossover from Interferon Alfa Plus Cytarabine Yields High Rates of Durable Response: Results from the International Randomized Study of Interferon vs STI571 (IRIS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2137-2137
Author(s):  
Francois Guilhot ◽  
Keyword(s):  
Overall Survival ◽  
Median Time ◽  
Randomized Study ◽  
Interferon Alfa ◽  
Long Term Results ◽  
Newly Diagnosed ◽  
Durable Response ◽  
Loss To Follow Up ◽  
The Status

Abstract Imatinib (IM) and interferon alfa plus cytarabine (IFN+Ara-C) were compared in the phase 3 IRIS trial, which enrolled 1106 patients (pts) with newly diagnosed CML-CP. Pts were allowed to cross over to the alternative treatment arm provided intolerance to treatment was indicated and/or efficacy landmarks were not met. All crossover requests required approval by the Study Management Committee according to strict criteria. Reasons for crossover were amended during the trial to include reluctance to continue IFN+Ara-C. The status of the 553 pts randomly assigned to receive 1st-line IFN+Ara-C and the reasons for crossover to IM are summarized in Table 1. Table 1: Status of IFN + Ara-C pts* Randomly assigned to 1st-line IFN + Ara–C N = 553 * Analysis as of 31-Jan-06 On 1st-line IFN + Ara-C 16 (2.9%) Discontinued from the study 178 (32.2%) Crossed over to IM 359 (64.9%) – Intolerance of treatment 144 (26%) – No CHR at 6 or 12 mos 44 (8.0%) – No MCyR at 12 or 24 mos 53 (9.6%) – Reluctance to continue on IFN + Ara-C 41 (7.4%) – Progression 77 (13.9%) = Increase in WBC 25 (4.5%) = Loss of CHR 29 (5.2%) = Loss of MCyR 23 (4.2%) On 2nd-line IM at 60 mos 251 (45.4%) The median time on IFN+Ara-C treatment before crossover was 9 months (mos), the median time since diagnosis was 13 mos at start of 2nd-line IM. The median time on 2nd-line IM was 45 mos (average 40 mos), with a maximum of 63 mos as per data cutoff 31-Jan-06. About one third of pts discontinued 2nd-line therapy: reasons were unsatisfactory therapeutic effect (13%), adverse events (4%), death (1%) and others (12%) including withdrawal of consent, BMT, loss to follow-up. A total of 251 pts remain on 2nd-line IM. Among 359 pts treated with 2nd-line IM, the best observed CHR rate was 93%, the best observed MCyR rate was 86%, and the best observed CCyR rate was 80%. The CCyR rate was 95% in pts who were reluctant to continue on IFN+Ara-C arm, 82% in intolerant pts, 78% in pts with lack of response on IFN+AraC and 71% in pts who progressed on 1st-line IFN+Ara-C. After 18 mos of 2nd-line IM therapy, the estimated rate of freedom from progression to AP/BC was 94%, and the estimated overall survival rate was 97%. These data are consistent with a previous trial of IM in pts with CML-CP after failure of prior IFN in which an estimated 89% of pts were free from progression to AP/BC, and an estimated 95% were alive, after 18 mos (Kantarjian NEJM 2002). In this trial, median time from diagnosis and median duration of prior IFN therapy were 34 and 14 mos, respectively. Table 2 compares 1st-line and 2nd-line IM results in the IRIS trial. Table 2: Comparison of Long-Term Results at 48 mos* 1st-line IM (N= 553) % [CI] 2nd-line IM (N=359) % [CI] * Analysis as of 31-Jan-06 Estimated survival w/o progression to AP/BC 93.3 % [91, 96] 90.3% [86, 94] Estimated overall survival 90.4% [87, 93] 89.2% [85, 93] The 48-mos rates of freedom from progression to AP/BC (overall survival) were 97% (96%) in pts who were reluctant to continue on IFN+Ara-C arm, 93% (90%) in intolerant pts, 90% (88%) in pts with lack of response on IFN+Ara-C and 80% (85%) in pts who progressed 1st-line IFN+Ara-C. The adverse event profile was similar between 1st- and 2nd-line IM therapy. CML-CP pts treated with 2nd-line IM after IFN+Ara-C achieved high response rates that are durable; the vast majority of pts remain free from progression to AP/BC after median follow-up of nearly 4 years. However, the overall efficacy results were better for 1st-line IM pts in newly diagnosed CML-CP.

Prostate-directed radiation therapy and overall survival for men with M1a prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 101-101
Author(s):  
David Dewei Yang ◽  
Santino Butler ◽  
Vinayak Muralidhar ◽  
Brandon Arvin Virgil Mahal ◽  
Neil E. Martin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Confidence Interval ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Gleason Grade ◽  
Newly Diagnosed ◽  
Metastatic Burden

101 Background: A recent randomized controlled trial demonstrated that radiation therapy to the prostate improves overall survival for men with newly diagnosed metastatic prostate cancer with a low metastatic burden. Most patients in this trial had bony metastases (stage M1b). The benefit of prostate-directed radiation therapy for men with metastases limited to non-regional lymph nodes (stage M1a) is unknown. We investigated the association between prostate-directed radiation therapy and overall survival for men with M1a prostate cancer. Methods: We identified 2,079 men from the National Cancer Database who were newly diagnosed with M1a prostate adenocarcinoma from 2004 through 2014 and had data on the use of androgen deprivation therapy, chemotherapy, and radiation therapy. Median follow-up was estimated using the reverse Kaplan-Meier method. The association between radiation therapy to the prostate and overall survival was examined using multivariable Cox proportional hazards regression analysis. Results: Overall, 12.7% (264) of patients received radiation therapy to the prostate. Median follow-up was 4.6 years (95% confidence interval 4.3-4.8 years). On multivariable analysis, when accounting for the use of androgen deprivation therapy and chemotherapy, Gleason grade group, clinical tumor and nodal stage, and prostate-specific antigen level at diagnosis, the use of radiation therapy to the prostate was associated with a significant improvement in overall survival (adjusted hazard ratio 0.60, 95% confidence interval 0.49-0.74, P<0.001). Adjusted median overall survival was 3.3 years for patients who did not receive radiation therapy to the prostate compared to 5.5 years for patients who did. Conclusions: Similar to newly diagnosed M1b prostate cancer with a low metastatic burden, patients with M1a prostate cancer may also derive a significant overall survival benefit from receiving radiation therapy to the primary prostate tumor. The use of prostate-directed radiation therapy for M1a patients should be further investigated.

Bevacizumab in combination with radiotherapy plus concomitant and adjuvant temozolomide for newly diagnosed glioblastoma: Update progression-free survival, overall survival, and toxicity

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2017-2017 ◽  
Author(s):  
M. L. Gruber ◽  
S. Raza ◽  
D. Gruber ◽  
A. Narayana
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Similar Treatment ◽  
Macdonald Criteria ◽  
Newly Diagnosed Glioblastoma ◽  
Group A ◽  
Group B ◽  
Cycle Group

2017 Background: Prognosis of glioblastoma (GBM) is very poor. Standard treatment includes surgical resection (SR), radiation (RT), concomitant and adjuvant chemotherapy with temozolomide (TMZ). Our objective is to assess the treatment efficacy, safety and survival in patients with newly-diagnosed GBM treated with RT, TMZ, and bevacizumab in the upfront management. Methods: From 2006–2008, 51 eligible patients (age >18, KPS >70) with newly-diagnosed GBM divided into two groups. Group A (n = 20) was treated with RT (60Gy) and concomitant TMZ (75mg/m2 daily for 42 days) with bevacizumab (10mg/kg every 2 weeks), 29 days following surgery, followed by up to six cycles of adjuvant TMZ (150mg/m2,daily x 7d, q28 with bevacizumab at 10mg/kg days 8 and 22 of each 28 day cycle. Group B (n = 31) received similar treatment without bevacizumab. Both groups were followed up until tumor progression (PFS). Recurrence was defined according to MacDonald Criteria. The end points were PFS, overall survival (OS) and toxicity. Results: Median bevacizumab infusions were 12 (4–32). Median follow-up was14 months for both groups. 6 months PFS survival in Group A was 77.5% and in Group B was 51.6%. Median PFS in Group A was 17 months compared to 7 months in Group B (p < 0.0001, HR = 0.26). Median OS has not been reached in Group A and was 17 months in Group B. One and 2 year OS were 83% and 57% in Group A compared to 72% and 6.5% in Group B (p = 0.02) ). Post-RT and temodar toxicities include thrombocytopenia (1 patient; Gr 3 and fatigue (3 patient;1 Gr 3), bevacizumab related toxicities with RT include leg ulcer with cellulites (1 patient; Gr 3) and pulmonary embolism with thrombocytopenia (1 patient; Gr 4), hypertension (2 patients; Gr 1), and asymptomatic blood products on MRI (2 patients). Conclusions: Bevacizumab has demonstrated efficacy, acceptable toxicity, improved PFS and OS in the upfront management of GBM. No significant financial relationships to disclose.

RADT-22. CONCURRENT TTFIELDS (200 KHZ) WITH CHEMORADIATION FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MAY INCREASE THE RATE OF PSEUDOPROGRESSION: ANALYSIS OF A PILOT CLINICAL TRIAL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi45-vi46
Author(s):  
Muneeb Niazi ◽  
James Taylor ◽  
Ryan Miller ◽  
Ayesha S Ali ◽  
Voichita Bar-Ad ◽  
...  
Keyword(s):  
Median Time ◽  
Small Sample ◽  
Concurrent Chemoradiation ◽  
Tumor Board ◽  
Newly Diagnosed ◽  
Female Ratio ◽  
Radiology Reports ◽  
Newly Diagnosed Glioblastoma ◽  
Trimodality Treatment

Abstract OBJECTIVE The standard of care for the adjuvant treatment of glioblastoma is concurrent chemoradiation, maintenance temozolomide, and Tumor Treating Fields (TTFields). TTFields may reversibly impact the blood-brain barrier, most significantly at 100 kHz. We hypothesized that this may increase the rate of pseudoprogression (PsP) in patients who receive concurrent chemoradiation with TTFields (200 kHz). METHODS This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Patients with newly diagnosed glioblastoma, age ≥ 18 years, and KPS ≥ 60 were eligible. They received concurrent temozolomide (75 mg/m2), scalp-sparing radiation (60 Gy in 30 fractions), and TTFields (200 kHz). Radiation was delivered through the TTFields arrays. PsP was defined as radiographic progression of enhancing lesions without clinical decline that improved or remained stable upon subsequent imaging. The rate of PsP was determined by an evaluation of the 2nd MRI at our multidisciplinary tumor board after the completion of trimodality treatment. These findings were confirmed with official radiology reports. RESULTS 30 patients were enrolled. Of these, 29 had imaging available for evaluation. Male-to-female ratio was 20:10. Median follow-up was 11.6 months (1.6-22.4 months), median age was 58 years (19-77 years), and median KPS was 90 (70-100). 20 (66.7%) patients had unmethylated and 10 (33.3%) had methylated MGMT promotor. Median time from surgery to initiation of radiation was 34 days (26-49 days). Median time from completion of trimodality treatment to 2nd follow-up MRI was 90 days (29-109 days). 15/29 (51.7%) patients had PsP. Patients with methylated and unmethylated MGMT promotor had 50.0% (5/10) and 52.6% (10/19) rates of progression respectively. CONCLUSIONS 51.7% of the patients who received concurrent chemoradiation with TTFields demonstrated PsP. The incidence is greater than historical reports. However, these findings should be explored in larger cohorts as this study was limited by a small sample size.

Modified Topotecan Combination with Cyclophosphamide and Ara-C (CAT) for Patients with Refractory/Relapsed Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4357-4357
Author(s):  
Sui-jing Wu ◽  
Xin Du ◽  
Wei Lin ◽  
Zi-lun Huang ◽  
Xiao-li Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Survival Time ◽  
Median Time ◽  
Topoisomerase I ◽  
Median Overall Survival ◽  
Blast Phase ◽  
Platelet Recovery ◽  
Overall Survival Time ◽  
Median Overall Survival Time

Abstract The prognosis of patients with leukemia has improved significantly. With combination chemotherapy, 60%–80% of adult patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia(ALL) achieve complete remission(CR). But most patients eventually relapse and do not response to current induction regimens based on cytarabine and anthracyclines any more. This emphasize the need to discover new agents for the treatment of leukemia to improve long-term prognosis. Topotecan is a semisynthetic analogue of the alkaloid camptothecin which acts as a specific inhibitor of topoisomerase I,by stabilization of the topoisomerase I DNA complex which leads to cell death.It also appears to be active against leukemias which have acquired the multi-drug resistant phenotype.[ Ulukan et al. Drug, 2000; Weihrauch et al. Leuk Lymphoma, 2004].It also could go through blood brain barrier[Kollmannsberger et al. Oncology, 1999].Here we observe the effect and side-effects of cyclophosphamide, cytanthetic analogue of rabine and topotecan (Modified CAT) combination regimen for treatment of refractory or relapsed leukemia. The study population comprise 26 patients with relapsed/refractory leukemia,including 12 with AML, 9 with ALL, 2 with myeloid blast phase of CML, 3 with lymphoma. Median age was 35 years.Patients received cyclophosphamide 300mg/m2 every 12 hours for 6 doses on day1 to 3.On day 2, topotecan was given at a dose of 1.5mg/m2/day for 5 days on days 2 to 6, and cytarabine 1.0 g/m2 /day for 5 days on days 2 to 6.The regimen (cytarabine reduced to 0.5g/m2 /day) could be repeated one or two cycles after remission. The total response rate of one course was 57%, eleven patients (42%) achived complete remission(CR). Responses occurred in 7of 12 AML (57%), including 5 CR(41%); in 6 of 9 patients with ALL (67%), including 5 CR(56%); and in 1 of 2 myeloid blast phase of CML(CR 50%). The median overall survival time after treatment was 2+ months, and the median overall survival time after CR was 4+ months. Severe myelosuppression was universal (100% Grade 4 neutropenia and thrombocytopenia), the median time to recovery of neutrophils to ≥0.5×109/L was 18 days,and the median time to platelet recovery to ≥ 20×109/L was 26 days.Infection developed in 96% cases, the most frequent events were oral mucositis(77%, 20/26), sepedogenesis(46%, 12/26),anusitis(38%,10/26),pneumonia(31%, 8/26), two patients died of infection complications(8%). Non-hematologic toxicity was seen frequently in gastrointestinal but it was mild. Nausea and/or vomiting occurred in 13 patients(50%)with gradeI-II in all of them.Two patients(8%) had diarrhea and grade 1–2 in them. In summary, Modified CAT regimen is well tolerated and has significant anti-leukemia activity as salvage therapy for relapsed/refractory leukemia.

scholarly journals Multimodal imaging-defined subregions in newly diagnosed glioblastoma: impact on overall survival

2018 ◽  
Vol 21 (2) ◽  
pp. 264-273 ◽  
Author(s):  
Flóra John ◽  
Edit Bosnyák ◽  
Natasha L Robinette ◽  
Alit J Amit-Yousif ◽  
Geoffrey R Barger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multimodal Imaging ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma

scholarly journals Involvement of Indoleamine 2,3-Dioxygenase in Impairing Tumor-Infiltrating CD8+T-Cell Functions in Esophageal Squamous Cell Carcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Ge Zhang ◽  
Wan-Li Liu ◽  
Lin Zhang ◽  
Jun-Ye Wang ◽  
Miao-Huan Kuang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Squamous Cell ◽  
Tumor Immune Escape ◽  
Cell Functions ◽  
Indoleamine 2,3 Dioxygenase ◽  
Overall Survival Time

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8+tumour-infiltrating lymphocytes (CD8+TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8+TILs. Patients with high IDO expression and a low number of CD8+TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8+TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8+TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.

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