scholarly journals Impact of Recurrence Pattern in Patients Undergoing a Second Surgery for Recurrent Glioblastoma

Author(s):  
Francesco Pasqualetti ◽  
Nicola Montemurro ◽  
Isacco Desideri ◽  
Mauro Loi ◽  
Noemi Giannini ◽  
...  

Abstract Background. The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to examine the impact of different patterns of GBM failure on patients’ survival and second surgery outcomes.Methods. Overall survival was assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluate the differences between curves.Results. Contact with ventricles, a second surgery and meningeal spread had a statistically impact on patient survival after the diagnosis of GBM recurrence (P=0.032, P=0.019 and P<0.01, respectively). Patients with local recurrence had better survival than patients with non-local ones, 24.1 versus 18.2 months, respectively (P=0.015, HR=1.856 (1.130 -3.050). Considering the cohort as a whole, the second surgery conferred an advantage in recurrent survival respect to non-operated patients. However, this advantage was more evident in patients with local recurrence (P=0.002 with HR 0.212 (95% CI 0.081-0.552) and P=0.029 with HR=0.522 (95% CI 0.291-0.936), respectively). Conclusions. The local recurrence pattern could be a promising field of interest for patients with recurrent GBM suitable for a second surgery.

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi20-vi20 ◽  
Author(s):  
Christina Tsien ◽  
Stephanie Pugh ◽  
adam Dicker ◽  
Jeffrey Raizer ◽  
Martha Matuszak ◽  
...  

Abstract This study sought to determine whether re-irradiation (ReRT) and concurrent bevacizumab (BEV) improves overall survival (OS) compared to BEV alone in recurrent glioblastoma (GBM). Patients (pts) were randomized 1:1 to ReRT (35 Gy/10 fractions) plus BEV (IV 10 mg/kg q2 wks) vs. BEV alone. With 160 pts, there was 80% power to detect a 31% reduction in death hazard for BEV+RT at a one-sided significance level of 0.10 using a log rank test. OS and PFS were estimated by Kaplan-Meier and HRs estimated by exact binomial distribution. Objective response was assessed using MacDonald and RANO criteria. From 11/2012 to 4/2016, 182 pts were randomized, with 170 eligible, analyzable pts. 11 pts did not receive protocol treatment. Patient characteristics (age, KPS, re-resection rates) were balanced between arms. Median f/u for censored pts was 12.8 months (mos; min-max, 0.03–52.8). BEV+ReRT did not improve OS vs BEV alone, with median OS of 10.1 vs 9.7 mos, (HR=0.98, 95% CI=0.70–1.38, p=0.46). Median PFS for BEV+RT and BEV was 7.1 vs. 3.8 mos, respectively (HR=0.73, 95% CI=0.53–1.0, p=0.051). BEV+ReRT improved 6-mo PFS rate (PFS6): 54 vs. 29%, (HR=0.42, 95% CI=0.34–0.5, p=0.001). Overall, treatment was well tolerated: 5% acute and 0% delayed grade 3+ treatment-related AE. Most patients died from recurrent GBM. CONCLUSION: RTOG 1205 is the first, prospective, randomized multi-institutional study to evaluate the safety and efficacy of ReRT in recurrent GBM using modern RT techniques. Overall, ReRT was shown to be safe and well tolerated. BEV+ReRT did not demonstrate a benefit in OS but an improved PFS6, and clinically meaningful PFS improvement. Molecular correlates of response analyses are ongoing. Funded by U10CA180868, U10CA180822 from the National Cancer Institute.


Author(s):  
A Kilian ◽  
K Parvez ◽  
E Monsalves ◽  
S Larjani ◽  
G Klironomos ◽  
...  

Background: The impact of second surgery on recurrence remains unclear, with few definitive studies to date. This study sought to identify major predictors of survival after second surgery. Methods: A retrospective chart review was conducted for 21 patients who underwent elective surgery for GBM recurrence, at our institution, in the past 6 years. Kaplan Meier was applied to determine the significance of the variables on survival time. The Mann Whitney U test was used to determine whether the median survival time differed significantly between groups, for the factors of interest. Results: Among variables examined, age, less than ≥50 (P=0.04) was significant. Patients younger than 50, had a median survival period of 11.8 months, while patients, age 50 or older, survived a median time of 4.2 months. Though chemotherapy after reoperation was not found to statistically significantly extend survival time on Kaplan-Meier (P=0.08), the median survival time was found to be significantly higher in patients that received chemotherapy (10.6 months) after reoperation, compared with those who did not (3.9 months), using the Mann Whitney U test (P=0.05). Conclusions: These results confirm that younger patients survive longer after second surgery and indicate that a second round of chemotherapy may prolong survival.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1061-1061
Author(s):  
Wei-Wu Chen ◽  
Twan Ying Chang ◽  
Shu-Min Huang ◽  
Ching-Hung Lin ◽  
Chiun Hsu ◽  
...  

1061 Background: For anthracycline-naïve metastatic breast cancer (AN-MBC) patients, past evidence indicated that anthracyclines are beneficial in the first-two lines of palliative chemotherapy but with considerable toxicities. However, with the provision of newer chemotherapies, comparative studies addressing the efficacy between anthracyclines and non-anthracyclines in the first-two lines of palliative chemotherapy for AN-MBC were lacking. Methods: We collectedclinicopathological characteristics of AN-MBC patients who had received palliative chemotherapy in National Taiwan University Hospital between 2001 and 2006. Patients were classified as anthracycline or non-anthracycline group according to the first-two lines of chemotherapy. Kaplan-Meier method and log-rank test were used for the estimation and comparison of both overall survival (OS) and time to treatment failure of the first-two lines (TTF2).Cox proportional hazard model was used for OS and TTF2. Best composite response rate (BCRR) were compared with logistic regression test. Results: A total of 109 (43.1%) patients in the anthracycline group and 144 (56.9%) patients in non-anthracycline group were analyzed. Between these two groups, the distributions of clinicopathological variables were generally similar and their median OS (33.3 vs 34.2 months, p = 0.179), TTF2 (13.3 vs 12.7 months, p = 0.104), and BCRR (59.5 vs 61.1%, p = 0.81) were not significantly different. Subgroup analysis showed that patients in the anthracycline group had a trend toward better OS in the estrogen receptor (ER) negative/ human epidermal growth factor receptor type II (HER2) positive subtype (median OS 58.0 vs 31.2 months, p = 0.081). In multivariate analysis, patients in the anthracycline group had a trend toward better OS (HR 0.72, 95% CI 0.52 - 1.00, p = 0.052). However, the exclusion of ER-/Her2+ subtype attenuated the impact of early anthracycline treatment on OS (HR 0.82, 95% CI 0.56 - 1.18, p = 0.28). Conclusions: Our study demonstrated that anthracyclines may not be mandatory in the first-two lines of palliative chemotherapy for AN-MBC but may be more beneficial to ER-/Her2+ subtype patients.


2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.


Author(s):  
Francesco Pasqualetti ◽  
Nicola Montemurro ◽  
Isacco Desideri ◽  
Mauro Loi ◽  
Noemi Giannini ◽  
...  

2021 ◽  
Author(s):  
Yuichi Kojima ◽  
Sho Nakakubo ◽  
Keisuke Kamada ◽  
Yu Yamashita ◽  
Nozomu Takei ◽  
...  

SummaryBackgroundAlthough biological agents, tocilizumab and baricitinib, have been shown to improve the outcomes of patients with COVID-19, a comparative evaluation has not been performed.MethodsA retrospective, single-center study was conducted using the data of patients with COVID-19 admitted to the Hokkaido University hospital between April 2020 and September 2021, who were treated with tocilizumab or baricitinib. The clinical characteristics of patients who received each drug were compared. Univariate and multivariate logistic regression models were performed against the outcomes of all-cause mortality and the improvement in respiratory status. The development of secondary infection events was analyzed using the Kaplan–Meier analysis and the log-rank test.ResultsThe use of tocilizumab or baricitinib was not associated with all-cause mortality and the improvement in respiratory status within 28 days of drug administration. Age, chronic renal disease, and comorbid respiratory disease were independent prognostic factors for all-cause mortality, while anti-viral drug use and severity of COVID-19 at baseline were associated with the improvement in respiratory status. There was no significant difference in the infection-free survival between patients treated with tocilizumab and those with baricitinib.ConclusionThere were no differences in efficacy and safety between tocilizumab and baricitinib for the treatment of COVID-19.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Takaya Kitano ◽  
Tsutomu Sasaki ◽  
Yasufumi Gon ◽  
Kenichi Todo ◽  
Shuhei Okazaki ◽  
...  

Introduction: Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We aimed to clarify the impact of chemotherapy on stroke risk in cancer patients. Methods: We investigated 27,932 patients enrolled in a hospital-based cancer registry at Osaka University Hospital between 2007 and 2015. The registry collects clinical data, including cancer status (site and stage), on all patients treated for cancer. Of them, 19,006 patients with complete data were included. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. Results: Of the 19,006 patients, 5,887 (31%) patients were in the chemotherapy group. Non-targeted chemotherapy was used in 5,371 patients. Stroke occurred in 44 patients (0.75%) in the chemotherapy group and 51 patients (0.39%) in the no-chemotherapy group. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than patients in the no-chemotherapy group (HR 1.84; 95% CI 1.23-2.75; Figure [A]). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91; Figure [B]). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). These findings were consistent with analysis wherein the effect of chemotherapy was treated as a time-dependent covariate (HR 1.02; 95% CI 0.55-1.88). Conclusions: In this population, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii80-iii80
Author(s):  
M Yahia-Cherif ◽  
O De Witte ◽  
C Mélot ◽  
F Lefranc

Abstract BACKGROUND The aim of this study was i) to analyse the effect of repeat surgeries on the survival of patients with focally recurrent glioblastoma who have benefited from temozolomide treatment and ii) to identify potential prognostic factors for survival. MATERIAL AND METHODS Cases from 2005 to 2014 in the glioblastoma database of our department were retrospectively reviewed. The Kaplan-Meier method was used to estimate overall survival (OS) as a function of time after one, two and three surgical resections. All patients received the standard of care after the first surgery (temozolomide during and after radiotherapy) and adjuvant treatment after repeat surgeries. RESULTS One hundred-thirty-two glioblastoma patients (median age: 57 years) were included in the study. Among them, 68, 53 and 11 patients underwent one, two and three surgical resections, respectively. The median OS was 11, 16 and 18 months, respectively, for patients who underwent one, two and three surgical resections. Patients who underwent two (p<0.001) or three (p<0.01) surgeries survived significantly longer than patients who underwent only one. No significant difference was observed between patients who underwent two versus three surgeries (p=0.76). A second resection performed more than 6 months after the initial resection was the only factor associated with prolonged survival (p=0.008). CONCLUSION Glioblastoma patients who benefited from temozolomide treatment and underwent surgery for recurrent glioblastoma exhibited a significant increase in survival compared with patients who did not undergo a second surgery. By contrast, a third surgery for a second recurrence did not contribute to any significant survival benefit.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Kyle W Singleton ◽  
Alyx B Porter ◽  
Leland S Hu ◽  
Sandra K Johnston ◽  
Kamila M Bond ◽  
...  

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.


2019 ◽  
Vol 145 (3) ◽  
pp. 531-540
Author(s):  
Wolfgang Wick ◽  
Andriy Krendyukov ◽  
Klaus Junge ◽  
Thomas Höger ◽  
Harald Fricke

Abstract Purpose Glioblastoma is an aggressive malignant cancer of the central nervous system, with disease progression associated with deterioration of neurocognitive function and quality of life (QoL). As such, maintenance of QoL is an important treatment goal. This analysis presents time to deterioration (TtD) of QoL in patients with recurrent glioblastoma receiving Asunercept plus reirradiation (rRT) or rRT alone. Methods Data from patients with a baseline and ≥ 1 post-baseline QoL assessment were included in this analysis. TtD was defined as the time from randomisation to the first deterioration in the EORTC QLQ-C15, PAL EORTC QLQ-BN20 and Medical Research Council (MRC)-Neurological status. Deterioration was defined as a decrease of ≥ 10 points from baseline in the QLQ-C15 PAL overall QoL and functioning scales, an increase of ≥ 10 points from baseline in the QLQ-C15 PAL fatigue scale and the QLQ-BN20 total sum of score, and a rating of “Worse” in the MRC-Neurological status. Patients without a deterioration were censored at the last QoL assessment. Kaplan–Meier estimates were used to describe TtD and treatment groups (Asunercept + rRT or rRT alone) were compared using the log-rank test. Results Treatment with Asunercept + rRT was associated with significant improvement of TtD compared with rRT alone for QLQ-CL15 PAL overall QoL and physical functioning, and MRC Neurological Status (p ≤ 0.05). In the Asunercept + rRT group, QoL was maintained beyond progresison of disease (PoD). Conclusion Treatment with Asunercept plus rRT significantly prolongs TtD and maintains QoL versus rRT alone in recurrent glioblastoma patients.


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