scholarly journals Outcomes of Salvage Fractionated Reirradiation Combined With Bevacizumab for Recurrent High-grade Gliomas That Progressed After Treatment With Bevacizumab

2021 ◽  
Author(s):  
Hajime Yonezawa ◽  
Makoto Ohno ◽  
Hiroshi Igaki ◽  
Yasuji Miyakita ◽  
Masamichi Takahashi ◽  
...  
Keyword(s):  
Gastrointestinal Haemorrhage ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
Mutation Status ◽  
Free Survival ◽  
Not Otherwise Specified ◽  
Radiological Response ◽  
High Grade Gliomas ◽  
Grade 3

Abstract Background: This study evaluated the outcomes of reirradiation combined with bevacizumab (Bev) for patients with recurrent high-grade gliomas that progressed after treatment with Bev.Methods: Between January 2015 and September 2019, 14 patients who experienced progression after Bev treatment were treated with reirradiation consisting of 25 Gy in five fractions combined with Bev (ReRT/Bev). The isocitrate dehydrogenase (IDH) 1/2 mutation status was analysed by pyrosequencing. Results: The diagnoses of 14 patients at the time of reirradiation included six cases of glioblastoma (GBM) with IDH-wildtype, four cases of GBM with IDH-mutant, one case of anaplastic astrocytoma (AA) with IDH-wildtype, one case of AA with IDH-mutant, and one case of GBM not otherwise specified (NOS), and one case of radiologically diagnosed brainstem glioma. The median overall survival (OS) and progression-free survival (PFS) times with ReRT/Bev were 6.1 months and 3.8 months, respectively. The 6-month OS and PFS rates were 54.5% and 15.7%, respectively. The median OS and PFS did not differ significantly between patients with IDH-wildtype (N=7) and IDH-mutant (N=5) (OS: 7.3 [wildtype] vs 6.0 [mutant] months, p = 0.64; PFS: 3.8 [wildtype] vs 3.7 [mutant] months, p = 0.56). The median OS and PFS did not differ significantly between patients with a diagnosis of GBM (N=6) and those with a diagnosis of non-GBM (N=7) (OS: 9.3 [GBM] vs 6.0 [non-GBM] months, p = 0.19; PFS: 4.0 [GBM] vs 3.8 [non-GBM] months, p = 0.31). Four patients (28.6%) achieved a complete or partial radiological response and three patients (21.4%) experienced improvement after ReRT/Bev. Tumor recurrences were observed in 12 patients, including 3 (21.4%) in-field recurrence; 5 (35.7%) marginal recurrence, 3 (21.4%) out-field recurrence, and 1 (7.1%) had in-field and out-field recurrence. Grade 3/4 toxicities included leukopenia in four patients (28.6%), hypertension in three (21.4%), proteinuria in one (7.1%), and gastrointestinal haemorrhage in one (7.1%) with ReRT/Bev. Conclusions: ReRT/Bev for patients with high-grade glioma who experienced progression after Bev was effective and involved acceptable toxicities.

scholarly journals Anlotinib Alone or in Combination With Temozolomide in the Treatment of Recurrent High-Grade Glioma: A Retrospective Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qunying Yang ◽  
Chengcheng Guo ◽  
Xiaoping Lin ◽  
Lili Luo ◽  
Zhenqiang He ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Rank Test ◽  
Cancer Center ◽  
High Grade ◽  
Karnofsky Score ◽  
Free Survival ◽  
Grade 3

Background: Anlotinib is a multi-target anti-angiogenic agent. This retrospective study aimed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide for the treatment of recurrent high-grade glioma.Materials and Methods: The clinical data of patients with recurrent high-grade glioma treated with anlotinib alone or in combination with temozolomide in our cancer center were collected and analyzed. Treatment response was evaluated according to the response assessment for neuro-oncology criteria. Progression-free survival, progression-free survival at 6 months, overall survival, and overall survival at 12 months were evaluated by Kaplan–Meier method and compared by log-rank test.Results: Between August 2019 and December 2020, 31 patients with recurrent high-grade glioma (21 of grade 4 and 10 of grade 3) were enrolled in this study. Seventeen patients received anlotinib alone and 14 received anlotinib plus temozolomide. All patients were heavily treated, the median lines of previous treatments were 2, and the median Karnofsky score was 60. At the data cutoff date, the median progression-free survival was 4.5 months and the progression-free survival at 6 months was 43.5%. The median overall survival was 7.7 months, and the overall survival at 12 months was 26.7%. The progression-free survival at 6 months and the overall survival at 12 months for 21 patients with grade 4 glioma was 40.2 and 27.9%, respectively. The tumor objective response rate was 41.9% in all patients and 33.3% in patients with grade 4 glioma. No grade 3 or worse treatment-related adverse events were recorded during the treatment.Conclusion: Anlotinib alone or in combination with temozolomide showed encouraging efficacy and favorable tolerability in patients with recurrent high-grade glioma who had been heavily treated.

Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17552-e17552
Author(s):  
Rodrigo Sanchez-Bayona ◽  
Pablo Tolosa ◽  
Ana Sanchez de Torre ◽  
Alicia Castelo ◽  
Elsa Bernal-Hertfelder ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
High Grade ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Platinum Resistant ◽  
Heavily Pretreated ◽  
Grade 3

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.

scholarly journals Hypofractionated Stereotactic Re-Irradiation with Pembrolizumab and Bevacizumab in Patients with Recurrent High Grade Gliomas: Results from a Phase 1 Study

2020 ◽  
Author(s):  
Solmaz Sahebjam ◽  
Peter A Forsyth ◽  
Nam D Tran ◽  
John A Arrington ◽  
Robert Macaulay ◽  
...  
Keyword(s):  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
High Grade ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

Abstract Background Radiotherapy may synergize with programmed death 1 (PD-1)/PD-1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended Phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD-1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high grade gliomas (HGGs). Methods Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W. Results Thirty two patients were enrolled (bevacizumab naïve, n = 24; bevacizumab resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab naïve cohort, twenty patients (83%) had a complete response (CR) or partial response (PR). The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (20/26 pts; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression &lt;1%. Conclusions The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.

Measuring response to neoadjuvant chemotherapy in high-grade serous tubo-ovarian carcinoma: an analysis of the correlation between CT imaging and chemotherapy response score

2019 ◽  
Vol 29 (5) ◽  
pp. 929-934 ◽  
Author(s):  
Meabh McNulty ◽  
Adarsh Das ◽  
Paul A Cohen ◽  
Andrew Dean
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Partial Response ◽  
Stable Disease ◽  
Progression Free Survival ◽  
Chemotherapy Response ◽  
High Grade ◽  
Free Survival ◽  
Radiological Response ◽  
Response Score

IntroductionResponse to neoadjuvant chemotherapy is measured by CT and the decision to proceed with interval surgery is made on the radiological response after two or three cycles of therapy. The Chemotherapy Response Score grades histological tumor regression in omental metastases resected at interval surgery and is associated with progression-free survival and overall survival. It is uncertain whether radiological response is associated with prognosis and whether radiological response predicts Chemotherapy Response Score.To assess if radiological response is associated with progression-free survival and overall survival. Additionally, to investigate whether radiological response predicts the Chemotherapy Response Score.MethodsRetrospective cohort study of patients with high-grade serous ovarian cancer treated with neoadjuvant chemotherapy. Radiological response was assessed by comparing CT imaging at baseline and after neoadjuvant chemotherapy using RECIST (Response Evaluation Criteria In Solid Tumors) and classified as stable disease, partial response, complete response, or progressive disease. Survival analysis was performed using Cox proportional-hazard models and the log-rank test.ResultsA total of 71 patients met the inclusion criteria. Of these, 51 had pre- and post-neoadjuvant chemotherapy CT scans available for analysis. Radiological response was not associated with progression-free survival or overall survival on univariate analysis (stable disease vs partial response; HR for progression-free survival 1.15; 95% CI 0.57 to 2.32; p = 0.690; HR for overall survival 1.19; 95% CI 0.57 to 2.46; p = 0.645). In a multivariate model, radiological response was not associated with either progression-free survival (stable disease vs partial response; HR=1.19; 95% CI 0.498 to 2.85; p = 0.694) or overall survival (stable disease vs partial response; HR=0.954; 95% CI 0.38 to 2.40; p = 0.920). There was a significant association between the Chemotherapy Response Score and radiological response (p = 0.005).DiscussionA partial response and stable disease on radiological assessment after neoadjuvant chemotherapy in women with advanced high-grade serous ovarian cancer were not associated with survival, despite having a correlation with the Chemotherapy Response Score.

scholarly journals Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas

2008 ◽  
Vol 10 (2) ◽  
pp. 162-170 ◽  
Author(s):  
Kathleen R. Lamborn ◽  
W. K. Alfred Yung ◽  
Susan M. Chang ◽  
Patrick Y. Wen ◽  
Timothy F. Cloughesy ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
High Grade ◽  
Free Survival ◽  
End Point ◽  
High Grade Gliomas

scholarly journals Prognostic Value of Metabolic Tumor Volume on 11C-Methionine PET in Predicting Progression-Free Survival in High-Grade Glioma

2015 ◽  
Vol 49 (4) ◽  
pp. 291-297 ◽  
Author(s):  
Min Young Yoo ◽  
Jin Chul Paeng ◽  
Gi Jeong Cheon ◽  
Dong Soo Lee ◽  
June-Key Chung ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Metabolic Tumor Volume ◽  
High Grade ◽  
Free Survival

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience

2020 ◽  
pp. 107815522092068
Author(s):  
Ozkan Alan ◽  
Tugba Akin Telli ◽  
Tugba Basoglu Tuylu ◽  
Rukiye Arikan ◽  
Nazım Can Demircan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Idh1 Mutation ◽  
High Grade ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Ecog Ps

Purpose Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. Methods Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. Results At the time of diagnosis, the median age was 48 (17–77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1–68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). Conclusion Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.

Phase I study of erlotinib administered concurrently with and after irradiation (RT) in the treatment of children, adolescents, and young adults with newly diagnosed intracerebral high-grade glioma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9553-9553
Author(s):  
A. Broniscer ◽  
S. J. Baker ◽  
T. E. Merchant ◽  
F. H. Laningham ◽  
M. Kocak ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
High Grade Glioma ◽  
Maximum Tolerated Dose ◽  
Exclusion Criterion ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3

9553 Background: High-grade gliomas are uncommon neoplasms in childhood that portend a poor prognosis. Because of the promising activity of erlotinib in adults with high-grade glioma, we conducted this Phase I study to determine the maximum tolerated dose and dose limiting toxicity (DLT) of erlotinib administered concurrently with and after RT. Methods: Patients between 3 and 25 years of age with newly diagnosed high-grade glioma received erlotinib continuously once daily during and after RT for a maximum of 52 weeks. Pharmacokinetic studies of erlotinib and its metabolite OSI-420, and genotyping were performed during course 1 in consenting patients. Use of enzyme-inducing anticonvulsants was an exclusion criterion. Dose escalation followed a typical Phase I design (dosage levels of 70, 90, and 120 mg/m2 per day). The DLT-evaluation period comprised the first 8 weeks of erlotinib. Results: Seventeen patients (median age 10.4 yrs; 10 males) were enrolled. Diagnoses consisted of glioblastoma (n=9), anaplastic astrocytoma (n=4), and other high-grade gliomas (n=4). Two of seven patients experienced reversible grade 3 hypokalemia / hypophosphatemia at the 70 mg/m2 level. Once electrolyte abnormalities were excluded as DLT, only one of seven patients at the 120 mg/m2 level has experienced grade 3 diarrhea so far. Pharmacokinetic studies were obtained in 14/17 patients. At the 70 mg/m2 dosage level, the median (range) erlotinib and OSI-420 Cmax and Tmax were 1,405 ng/ml (937–2,180) and 4.1 hr (2.2–8.2) and 158.5 ng/ml (45–203) and 4.1 hr (2.2–7.9), respectively. Three patients have received erlotinib for more than 1 year with disease stabilization. Six patients have already experienced disease progression. Conclusions: Erlotinib administered concurrently with RT on this schedule has been well tolerated. Preliminary pharmacokinetic results are comparable to those observed in adults. Rather than continue to escalate erlotinib dosages, we plan to complete this study and open a phase II study of erlotinib and RT for this same patient population. No significant financial relationships to disclose.

Expression of CD40 Correlates Negatively with Overall and Progression-Free Survival of Low- and High-Grade Gliomas

2019 ◽  
Vol 130 ◽  
pp. e17-e25
Author(s):  
Jan-Michael Werner ◽  
Saskia Kuhl ◽  
Katharina Ulrich ◽  
Boris Krischek ◽  
Pantelis Stavrinou ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
High Grade ◽  
Free Survival ◽  
High Grade Gliomas

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival

2009 ◽  
Vol 110 (1) ◽  
pp. 173-180 ◽  
Author(s):  
Ashwatha Narayana ◽  
Patrick Kelly ◽  
John Golfinos ◽  
Erik Parker ◽  
Glyn Johnson ◽  
...  
Keyword(s):  
Patient Survival ◽  
Chemotherapeutic Agent ◽  
Antiangiogenic Therapy ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Median Number ◽  
Antiangiogenic Agents ◽  
High Grade ◽  
Diffuse Disease ◽  
High Grade Gliomas

Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/ kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1–19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1–7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3–7.7) and 9 (95% CI 7.6–10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored.

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