scholarly journals Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Kyle W Singleton ◽  
Alyx B Porter ◽  
Leland S Hu ◽  
Sandra K Johnston ◽  
Kamila M Bond ◽  
...  
Keyword(s):  
Treatment Response ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Response To Therapy ◽  
Cytotoxic Therapy ◽  
Kaplan Meier ◽  
Recurrent Gbm

Abstract Background Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. Methods DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. Results In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. Conclusion DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

scholarly journals Days Gained Response Discriminates Treatment Response in Patients with Recurrent Glioblastoma Receiving Bevacizumab-based Therapies

2019 ◽  
Author(s):  
Kyle W. Singleton ◽  
Alyx B. Porter ◽  
Leland S. Hu ◽  
Sandra K Johnston ◽  
Kamila M. Bond ◽  
...  
Keyword(s):  
Treatment Response ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Response To Therapy ◽  
Cytotoxic Therapy ◽  
Kaplan Meier ◽  
Recurrent Gbm

AbstractPurposeAccurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma multiforme (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze Days Gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies.Experimental DesignDays Gained response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N=62). Kaplan-Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM.ResultsIn patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan-Meier analysis showed significant differences in OS and PFS at previously identified DG cutoffs consistent with previous DG analyses using gadolinium-enhanced T1 weighted MR imaging. DG scores for bevacizumab monotherapy only approached significance for PFS. Cox regression showed that increases of 25 DG were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy.ConclusionDays Gained has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

Evaluation of glioblastoma tumor microenvironment after treatment with pembrolizumab.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2559-2559 ◽  
Author(s):  
Nazanin Majd ◽  
Heather Y. Lin ◽  
Ying Yuan ◽  
Kristin Alfaro-Munoz ◽  
Kathy Hunter ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
T Cell Response ◽  
Rank Test ◽  
Recurrent Gbm

2559 Background: Neoadjuvant pembrolizumab improved outcome of patients with recurrent Glioblastoma (GBM) in two early phase clinical trials. However, several large phase II/III studies in patients with newly diagnosed and recurrent GBM failed to demonstrate a therapeutic benefit of anti-PD-1 therapy. Therefore, identification of biomarkers of response is crucial for appropriate patient selection and further clinical development of anti-PD-1 therapy. We reported the outcome of our window-of-opportunity clinical trial of neoadjuvant pembrolizumab in 15 patients with recurrent GBM, demonstrating rare CD8+ T cells and abundant of CD68+ macrophages in GBM tissue after 3 weeks of anti-PD-1 treatment (NCT02337686). In the current study, we compared tumor infiltrating lymphocyte (TIL) and PD-L1 scores, known biomarkers of response to anti-PD-1 therapy in other cancers, in pre-trial vs. on-trial tumor tissue and associated these markers with survival. Methods: We determined TIL score (morphological assessment of the presence or absence of TILs, 0-3) and PD-L1 H score (defined as [1*1+ %]+[2*2+ %]+[3*3+ %], 0-200) and correlated these with survival. The Wilcoxon signed rank test was used to compare levels of PD-L1 H or TIL scores between pre-trial and on-trial specimens. The Cox proportional hazards models were used to assess associations between correlative markers and progression free survival or overall survival (OS). Results: The on-trial TIL level (median: 3) was significantly higher than the pre-trial TIL level (median: 1) (p = 0.031). However the difference between pre-trial and on-trial PD-L1 levels was not statistically significant (p > 0.9). Patients whose on-trial PD-L1 H score was ≥ 3 trended toward a longer OS than those with a PD-L1 H score < 3 (HR [95% CI] = 0.225 [0.043, 1.183]) (p = 0.0782). Conclusions: Although GBM tissue lacks abundant T cells, treatment with pembrolizumab increases trafficking of T cells to the tumor microenvironment, which is necessary but not sufficient to induce an effector T-cell response. Elevated PD-L1 expression may be a biomarker of response to anti-PD1 therapy in GBM, which needs confirmation in larger studies. Further genomic, transcriptomic, and methylation profiling of the pre-trial and on-trial tissues is ongoing. Clinical trial information: NCT02337686 .

Histologic subtype and response to immune checkpoint inhibitor (ICI) therapy in advanced urothelial cancer (aUC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 495-495
Author(s):  
Natalie J. Miller ◽  
Ali Raza Khaki ◽  
Leonidas Nikolaos Diamantopoulos ◽  
Mehmet Asim Bilen ◽  
Victor Sacristan Santos ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Routine Practice ◽  
Histologic Subtype ◽  
Tract Cancer ◽  
Kaplan Meier ◽  
Urinary Tract Cancer ◽  
Tract Disease ◽  
Histologic Types

495 Background: Urinary tract cancer can be pure urothelial carcinoma (PUC) or variant UC (VUC, defined here as pure non-UC or mixed UC + non-UC); VUC often has a worse prognosis. Little is known about outcomes for patients (pts) with VUC receiving ICI. We hypothesized that VUC does not compromise ICI efficacy in pts with aUC. Methods: We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathologic, treatment and outcomes data was collected for pts with aUC who received ICI. Pts were stratified to PUC vs VUC; VUC was further divided by histologic subtype, i.e. squamous, neuroendocrine (NE), etc. We compared overall response rate (ORR) using logistic regression, progression free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox proportional hazards; p<0.05 was significant. Results: 519 consecutive pts were identified; 405, 414 and 411 included in ORR, OS and PFS analyses, respectively. Demographics included mean age 69, 27% female, 66% ever smokers, 15% upper tract disease, 54% with extirpative surgery. ORR to ICI between pts with PUC and VUC was comparable (both 28%, p=0.86) without significant differences for individual subtypes vs PUC. Median OS for pts with PUC was 11.0 vs 9.9 mo for VUC (p=0.45), but only 3.7 mo for those with NE features (HR=3.01 [95% CI 1.63-5.57] vs PUC, p<0.001). Median PFS was 4.1 vs 5.2 mo for PUC vs VUC (p=0.46) and 2.8 mo for NE (HR=1.85 [95% CI 0.94-3.61] vs PUC, p=0.07). Conclusions: ORR to ICI and OS were comparable across histologic types; however, OS was shorter for tumors with NE features. VUC should not exclude pts from receiving ICI in routine practice and clinical trials.[Table: see text]

scholarly journals Effect of Health Care Provider Delays on Short-Term Outcomes in Patients With Colorectal Cancer: Multicenter Population-Based Observational Study

10.2196/15911 ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. e15911
Author(s):  
Ahmed Abdulaal ◽  
Chanpreet Arhi ◽  
Paul Ziprin
Keyword(s):  
Colorectal Cancer ◽  
Observational Study ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Diagnostic Delay ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Treatment Delays ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Background The United Kingdom has lower survival figures for all types of cancers compared to many European countries despite similar national expenditures on health. This discrepancy may be linked to long diagnostic and treatment delays. Objective The aim of this study was to determine whether delays experienced by patients with colorectal cancer (CRC) affect their survival. Methods This observational study utilized the Somerset Cancer Register to identify patients with CRC who were diagnosed on the basis of positive histology findings. The effects of diagnostic and treatment delays and their subdivisions on outcomes were investigated using Cox proportional hazards regression. Kaplan-Meier plots were used to illustrate group differences. Results A total of 648 patients (375 males, 57.9% males) were included in this study. We found that neither diagnostic delay nor treatment delay had an effect on the overall survival in patients with CRC (χ23=1.5, P=.68; χ23=0.6, P=.90, respectively). Similarly, treatment delays did not affect the outcomes in patients with CRC (χ23=5.5, P=.14). The initial Cox regression analysis showed that patients with CRC who had short diagnostic delays were less likely to die than those experiencing long delays (hazard ratio 0.165, 95% CI 0.044-0.616; P=.007). However, this result was nonsignificant following sensitivity analysis. Conclusions Diagnostic and treatment delays had no effect on the survival of this cohort of patients with CRC. The utility of the 2-week wait referral system is therefore questioned. Timely screening with subsequent early referral and access to diagnostics may have a more beneficial effect.

scholarly journals Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma: A Comparison of PASS and GAPP Scoring Systems

2020 ◽  
Vol 105 (12) ◽  
pp. e4661-e4670
Author(s):  
Heather Wachtel ◽  
Troy Hutchens ◽  
Ezra Baraban ◽  
Lauren E Schwartz ◽  
Kathleen Montone ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Regression ◽  
Intraclass Correlation ◽  
Scoring Systems ◽  
Metastatic Potential ◽  
Disease Recurrence ◽  
Cox Proportional Hazards ◽  
Ki 67 ◽  
Kaplan Meier ◽  
Adrenal Pheochromocytoma

Abstract Purpose The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes. Methods The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan–Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS). Results From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low–moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P &lt; .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score. Conclusion Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.

Effect of baseline carbohydrate antigen 19-9 (CA19-9) level on overall survival (OS) in NAPOLI-1 trial: A phase III study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Li-Tzong Chen ◽  
Jens T Siveke ◽  
Andrea Wang-Gillam ◽  
Richard Hubner ◽  
Shubham Pant ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Effect ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Response To Therapy ◽  
Phase Iii ◽  
Free Survival ◽  
Previously Treated

425 Background: CA19-9 has been shown to correlate with response to therapy and OS in patients with mPAC. NAPOLI-1, a randomized phase 3 study evaluated nal-IRI, a nanoliposomal formulation of irinotecan, with or without 5-FU/LV vs 5-FU/LV in patients with mPAC previously treated with gemcitabine-based therapy. Nal-IRI+5-FU/LV significantly improved OS (primary endpoint) vs 5-FU/LV (6.1 mo vs 4.2 mo; unstratified hazard ratio [HR] = 0.67; P = 0.012). CA19-9 response (≥50% decline from baseline) was superior with nal-IRI+5FU/LV compared with 5-FU/LV (29% vs 9%; P=0.0006). Nal-IRI alone did not show a statistical improvement in survival. Methods: Patients with a recorded baseline CA19-9 measurement were divided into quartiles to evaluate the treatment effect pattern of CA19-9 from nal-IRI+5-FU/LV and 5-FU/LV arms. Quartile ranges were based on 404 available CA19-9 values from randomized patients (N=417). Unstratified Cox proportional hazards regression was used to estimate HRs and corresponding 95% CIs. Effect of baseline CA19-9 on time to response, progression-free survival, and response will be presented. Results: Of patients randomized to receive nal-IRI+5-FU/LV (n = 117) or 5-FU/LV enrolled contemporaneously (n = 119), 218 received study drug and had a baseline CA19-9 measurement. Results show a greater treatment effect on OS with higher CA19-9 level relative to 5-FU/LV. Conclusions: In patients with mPAC previously treated with gemcitabine-based therapy, nal-IRI+5-FU/LV significantly improved OS supported by progression free survival and objective response rate. The CA19-9 serum level can provide important information with regards to overall survival. Clinical trial information: NCT01494506. [Table: see text]

Early shifts in immune cell subsets to predict response to immune checkpoint blockade in non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 105-105 ◽  
Author(s):  
Samuel Rosner ◽  
Patrick M. Forde ◽  
Jarushka Naidoo ◽  
Kristen Marrone ◽  
Joshua E. Reuss ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Immune Cell ◽  
Acquired Resistance ◽  
Cell Subset ◽  
Immune Checkpoint Blockade ◽  
Cox Proportional Hazards ◽  
Response To Therapy ◽  
Rank Test ◽  
Targeted Agents ◽  
Kaplan Meier

105 Background: The use of immune targeted agents for NSCLC has improved outcomes for patients (pts) with metastatic disease. Biomarkers such as the neutrophil-to-lymphocyte ratio (NLR) prior to therapy have been shown to predict outcomes however little is known about dynamic changes in immune subset composition during therapy. Methods: A single institution, retrospective review was performed of 88 NSCLC pts who received anti-PD1 therapy. NLR and relative lymphocyte count (RLC) were recorded at baseline, 4 weeks after treatment initiation, and at every subsequent computed tomography scan until time of progression. Endpoints included overall survival (OS) and durable clinical benefit (DCB), defined as stable disease or response at 6 months after therapy. Non parametric tests were used to compare NLR and RLC between responders and non-responders, cox-proportional hazards regression analysis was used for univariate associations with OS and Kaplan-Meier survival curves were compared by the log-rank test. Results: Our cohort comprised of 60 male pts with a median age of 63 years and a median OS of 38.5 months. Baseline NLR and RLC were not associated with response to therapy (Mann Whitney p=0.25 and p=0.23, respectively). We identified a statistically significant higher RLC and lower NLR at week 4 in pts with DCB (Mann Whitney p=0.001). Continuous NLR and RLC values at 4 weeks were statistically significantly correlated with OS (HR=1.008, 95% CI 1.001-1.015, p=0.03 and HR=0.939, 95% CI 0.9-0.98, p=0.004 respectively). Using median RLC at 4 weeks as a threshold, pts with high RLC at 4 weeks had significantly favorable survival (log-rank p<0.0001). Using the previously reported cut-off point of NLR=4, pts with NLR>4 had significantly worse OS (log-rank p<0.0001). For pts with acquired resistance to therapy, RLC increased early during treatment followed by a decrease at the time of progression. Conclusions: Our findings suggest early immune cell subset dynamics are associated with clinical outcomes for NSCLC pts treated with anti-PD1 therapy. Our observations reflect the differential immune repertoire shifts and if prospectively validated may be used to stratify pts receiving immune targeted agents.

Outcomes and Prognostic Factors in Recurrent Glioma Patients Enrolled Onto Phase II Clinical Trials

1999 ◽  
Vol 17 (8) ◽  
pp. 2572-2572 ◽  
Author(s):  
Eric T. Wong ◽  
Kenneth R. Hess ◽  
Mary Jo Gleason ◽  
Kurt A. Jaeckle ◽  
Athanassios P. Kyritsis ◽  
...  
Keyword(s):  
Phase Ii ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioma ◽  
Dominant Factor ◽  
Karnofsky Performance Score ◽  
Phase Ii Trials ◽  
Recurrent Glioblastoma Multiforme

PURPOSE: To determine aggregate outcomes and prognostic covariates in patients with recurrent glioma enrolled onto phase II chemotherapy trials. PATIENTS AND METHODS: Patients from eight consecutive phase II trials included 225 with recurrent glioblastoma multiforme (GBM) and 150 with recurrent anaplastic astrocytoma (AA). Their median age was 45 years (range, 15 to 82 years) and their median Karnofsky performance score was 80 (range, 60 to 100). Prognostic covariates were analyzed with respect to tumor response, progression-free survival (PFS), and overall survival (OS) by multivariate logistic and Cox proportional hazards regression analyses. RESULTS: Overall, 34 (9%) had complete or partial response, whereas 80 (21%) were alive and progression-free at 6 months (APF6). The median PFS was 10 weeks and median OS was 30 weeks. Histology was a robust prognostic factor across all outcomes. GBM patients had significantly poorer outcomes than AA patients. The APF6 proportion was 15% for GBM and 31% for AA, whereas the median PFS was 9 weeks for GBM and 13 weeks for AA. Results were also significantly poorer for patients with more than two prior surgeries or chemotherapy regimens. CONCLUSION: Histology is a dominant factor in determining outcome in patients with recurrent glioma enrolled onto phase II trials. Future trials should be designed with separate histology strata.

scholarly journals Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1040
Author(s):  
Valérie Gounant ◽  
Michael Duruisseaux ◽  
Ghassen Soussi ◽  
Sylvie Van Hulst ◽  
Olivier Bylicki ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Cox Proportional Hazards ◽  
Poor Performance Status ◽  
Low Grade ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models

Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

scholarly journals Glioblastoma: Patterns of Recurrence and Efficacy of Salvage Treatments

2011 ◽  
Vol 38 (4) ◽  
pp. 621-625 ◽  
Author(s):  
Jiwon Oh ◽  
Arjun Sahgal ◽  
Paul Sanghera ◽  
May N. Tsao ◽  
Phil Davey ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Distant Recurrence ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Continuous Dose ◽  
Newly Diagnosed Glioblastoma

Abstract:Background:It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival.Methods:We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival.Results:58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61).Conclusion:The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.

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