Concurrent chemoradiation in the management of newly diagnosed glioblastoma multiforme: Retrospective review of single center experience over a period of 10 years.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14028-e14028
Author(s):  
Louise Price ◽  
Charlotte Ziff ◽  
Abdelfattah Elmasry ◽  
Selvaraj Giridharan

e14028 Background: Glioblastoma Multiforme (GBM) is the most common primary intracranial tumour of the brain. The standard of care first line management is maximum safe debulking followed by concurrent chemo radiation (Stupp et al, 2005). In spite of further recent advances, median survival still remains poor and ranges between 14 to 21 months, especially in the MGMT unmethylated group. There are no randomised trials investigating less than 6 cycles of adjuvant temozolomide (TMZ). In our study we retrospectively analyse the impact on overall survival (OS) and progression free survival (PFS) in cases where adjuvant treatment has been discontinued due to toxicity or patient’s fitness Methods: We collected data from 2007 to 2016 for a cohort of patients who underwent adjuvant treatment for GBM following histological diagnosis. The final analyses included patient’s who completed concurrent chemoradiotherapy to a dose of 60 Gray in 30 fractions and had at least one cycle of adjuvant TMZ chemotherapy Results: Of 110 patient cohorts, 57% of patients completed adjuvant chemo radiotherapy followed by 4-6 cycles of adjuvant TMZ, 43% received 3 or less cycles of TMZ. Overall PFS was 11.9 months. Those that completed 4 or more cycles of adjuvant TMZ had an improved PFS (Log rank test P-value 0.001) versus those that completed 3 or less cycles. On cox analysis the number of adjuvant cycles of TMZ significantly affects OS, P-value 0.0003. Median overall survival was 16 months for the whole group, but was 10 vs. 20 months for the two groups. On cox analysis we also identified second line chemotherapy had a significant impact on OS (cox model P-value 0.002) Conclusions: We identified patients receiving three or fewer cycles of adjuvant TMZ had poorer outcomes. Second-line chemotherapy improved outcomes at relapse regardless of redo surgery.

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi243-vi243
Author(s):  
Maeve Hennessy ◽  
Mohamed Dablouk ◽  
William Mullally ◽  
Philip O’Halloran ◽  
Stephen MacNally ◽  
...  

Abstract BACKGROUND While the treatment of primary Glioblastoma Multiforme (GBM) is well defined, the role of surgical resection in recurrent GBM is not firmly established.1 Treatment options for recurrent GBM include second-line chemotherapy, re-irradiation and surgical re-resection.2 This review examines current practice in a national neuro-oncology centre. AIMS: To investigate survival outcomes in patients undergoing surgical re-resection for recurrent GBM in our institution and to compare our findings to the relevant published literature. METHODS A retrospective review of our institution’s neuro-oncology database was performed. We evaluated all patients who underwent re-resection for recurrent GBM following standard adjuvant treatment between 2015–2018. Patients who did not have an initial diagnosis of Grade 4 GBM and patients who were re-operated on within one month were excluded. We analysed overall survival using Kaplan Meier curves. Patients not known to have died were censored to the last known alive date. We also examined factors which may affect patient outcome, including age, sex, extent of resection, tumour characteristics and tumour location. RESULTS 34 patients were eligible for inclusion into this study, of these 21 (61%) were male. Median age was 52. A radiologically confirmed initial resection of > 80% was achieved in 52% of patients. Median time from initial surgery to re-resection was 13.5 months. Median survival from initial surgery was 28.6 months and median survival after re-resection was 9.5 months. CONCLUSION Re-operation appears to have a role in the management of recurrent GBM in carefully selected cases. Overall survival in this patient cohort remains poor and further studies into the benefit of re-resection in comparison to second-line chemotherapy and re-irradiation would be of value.


Chemotherapy ◽  
2017 ◽  
Vol 62 (4) ◽  
pp. 205-213 ◽  
Author(s):  
Mie Kotake ◽  
Yosuke Miura ◽  
Hisao Imai ◽  
Keita Mori ◽  
Reiko Sakurai ◽  
...  

Background: In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. Methods: Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. Results: Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R2 = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R2 = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Conclusions: In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5151-5151
Author(s):  
Y. Loriot ◽  
C. Massard ◽  
A. Plantade ◽  
B. Escudier ◽  
A. Chauchereau ◽  
...  

5151 Background: There is currently no standard of care for patients (pts) with HRPC and disease progression after docetaxel-based chemotherapy. Platin compounds have demonstrated activity in this setting and in vitro evidence of synergy between carboplatin and etoposide has previously been reported. A significant proportion of advanced HRPC exhibit neuroendocrine features but there are limited data on whether these patients should be treated differently or not. Methods: Pts with HRPC who experienced failure after first-line docetaxel-based chemotherapy were prospectively treated with carboplatin (AUC 5 day 1) and etoposide (80 mg/m2 day 1 to 3), repeated every 3 weeks as second-line chemotherapy. The response rate (defined as a serum PSA decline of = 50%), progression-free survival (PFS) and overall survival (OS) were evaluated using consensus criteria (Bubley JCO 1999). Pain relief was evaluated using a visual analogic scale. Serum chromogranin A and neurone specific enolase (NSE) levels were measured at baseline. Toxicity was evaluated according to NCI criteria. Results: Forty-one HRPC pts, previously treated with docetaxel with (n=24) or without (n=17) estramustine, prospectively received carboplatin-etoposide as second-line chemotherapy. A PSA response was obtained in 9 pts (22%). Pain relief was achieved in 18 pts (45%). Median progression-free survival was 9 weeks and median overall survival was 19 months. Toxicity included grade 3–4 anemia in 25% and febrile neutropenia in 2%. Biological neuroendocrine features (e.g. elevated baseline serum chromogranin A and NSE) were not associated with response or PFS. The response rate was 18% and 31% in pts with normal and elevated baseline chromogranin A, respectively. Conclusions: The carboplatin-etoposide regimen is active and well-tolerated as second-line chemotherapy after docetaxel-based chemotherapy in HRPC patients. Activity was detected in both tumors with and without neuroendocrine features. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4067-4067
Author(s):  
Kohei Shitara ◽  
Keitaro Matsuo ◽  
Kei Muro ◽  
Atsushi Ohtsu

4067 Background: The correlation between progression-free survival (PFS) or time to progression (TTP) and overall survival (OS) has been evaluated in patients with advanced gastric cancer (AGC) who received first-line chemotherapy (Shitara, K et al. Invest New Drug 2011; Shitara K and Burzykowski T, et al, ASCO 2011). However, no corresponding analysis had been done in patients who underwent second-line chemotherapy for AGC. Methods: We evaluated the potential of PFS, TTP, response rate (RR), or disease control rate (DCR) to act as surrogates for OS in phase II and III trials of second-line chemotherapy for AGC by comprehensive literature-based analysis. Correlations between each endpoint and OS were evaluated by Spearman rank correlation coefficient (ρ). Subgroup analyses by trial region or type of failure to previous chemotherapy were also conducted. Results: Fifty-six trials, including four randomized studies, were selected for analysis and covered a total of 61 treatment arms and 3,038 patients; 34 studies were conducted in Asia, 20 studies in Non-Asian countries, and two studies in both regions. Median PFS were similar in Asian and Non-Asian trials (3.0 vs. 3.3 months). In contrast, median OS tended to be longer in Asian vs. Non-Asian trials (8.0 vs. 6.0 months; p<0.01). Median PFS/TTP and OS showed a moderate correlation with ρ of 0.51 (95% CI, 0.31-0.73). Correlation tended to be higher in PFS (ρ = 0.62) than TTP (ρ = 0.29) and higher in non-Asian trials (ρ = 0.73) than Asian trials (ρ = 0.32). Correlation between PFS/TTP and OS among the trials in which eligibility required failure to previous fluorouracil and cisplatin also showed low correlation (ρ = 0.48). The RR and DCR also did not show high correlation with OS (ρ = 0.30 for RR; 95% CI 0.04-0.56; ρ = 0.53 for DCR; 95% CI 0.31-0.75). The hazard ratio (HR) of PFS and OS in each arms of the four randomized studies showed a low correlation with ρ of 0.10. Conclusions: Our results indicate that PFS/TTP, RR, and DCR did not correlate sufficiently with OS to be used as surrogate endpoints in patients with AGC who underwent second-line chemotherapy. Further research is needed based on individual patient data from ongoing randomized trials.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15019-e15019 ◽  
Author(s):  
MinYuen Teo ◽  
Raymond S. McDermott

e15019 Background: Many clinicians adopt a nihilistic approach to the management of APC. Delivery of 2L-Ctx is relatively uncommon and no recognized standard exists. We sought to examine the published activity of chemotherapy in the 2nd line setting, and the rate of 2L-Ctx delivery and its influence on reported overall survival in 1st line trials. Methods: 1st and 2L-Ctx randomized trials published between 2000 and 2012 were identified from Pubmed, and manuscripts were obtained for data extraction. Pooled weighted objective response rates (ORR) and disease control rates (DCR) were calculated. For 1st line studies, the percentage of patients who received 2L-Ctx were extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Spearman correlation and linear regression were performed. Results: Sixty nine 2L Ctx studies (77 arms, n=2859) were identified. Majority received prior gemcitabine-based chemotherapy. Pooled ORR was 6.6% (95% CI 5.6 – 7.6%) and DCR was 36.7% (34.5 – 38.0%). When only prospective studies were evaluated (42 studies, 48 arms, n=1546), ORR was 5.0% (3.8 – 6.2%) and DCR was 33.9% (31.0 – 36.9%). Exploratory analysis suggested that intensification of gemcitabine-based therapy (ORR: 10.0%; DCR: 54.7%) might be marginally more active than fluoropyrimidine (7.6%; 32.2%) or taxane based 2L-Ctx (5.2%; 33.6%). 28/52 identified 1st line studies (54%) reported the percentage of patients treated with second-line chemotherapy (11 phase II, 28 arms, n=1450; 17 phase III, 33 arms, n=5051). Percentage of 2L-Ctx delivery ranged from 14 – 68% and correlated with OS (r=.49 [.26 – .67], p<.01) and PPS (r=.57 [.36 – .72], p<.01). When phase II studies were excluded, correlation was improved for OS (r=.63 [.35 – .81], p<.01) and PPS (r=.79 [.59 – .89], p<.01). Percentage of locally advanced disease did not correlate with OS/PPS nor affect prior analysis. Conclusions: Whilst awaiting further advancement in the 1st line setting, increased delivery of 2L-Ctx to patients with APC and maintained performance status may offer a survival benefit.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 450-450
Author(s):  
Nicha Wongjarupong ◽  
Mohamed Abdelrahim Muddathir Hassan ◽  
Cristobal T. Sanhueza ◽  
Mindy L. Hartgers ◽  
Fatima Hassan ◽  
...  

450 Background: The standard treatment for patients with gallbladder cancer is a combination of gemcitabine and cisplatin based on ABC-02 trial. However, there are no guidelines regarding treatment after first-line therapy. We retrospectively analyzed the efficacy and overall survival of different second-line regimens. Methods: We identified 203 patients with advanced gallbladder cancer who received palliative treatment between January 2000 and December 2015 at Mayo Clinic, Rochester. RECIST criteria was used to assess response. Results: 68 patients received second-line chemotherapy. Median age was 63 years (range: 32-86) and majority were males (60.6%). The median time from the diagnosis to the start of the second line chemotherapy was 8 (1-120) months. The most common used second-line chemotherapy were FOLFOX (14), gemcitabine alone (10), single agent fluoropyrimidine (11), gemcitabine with capecitabine (5), and capecitabine with oxaliplatin (4). There were 30 patients that received 5-fluorouracil based regimens, 20 patients received gemcitabine-based regimen, 3 patients received taxane-based regimen, and 15 patients received other types of chemotherapy. Median progression free survival and overall survival was 2.1 (1.8-2.7) and 16.7 (13.2-21.3) months respectively. There were 10 (52%), 11 (37%), 2 (67%), 5 (33%) with partial response and stable disease in 5-fluorouracil-based, gemcitabine-based, taxane-based, and others, respectively. There were no difference in PFS, with median PFS of 2.5, 2.0, 2.8 and 2.3 months, respectively (p=0.43). The overall survival were 15.7 (8.9-40.2), 15.0 (10.7-21.3), 40.3 (22.0-47.0), and 20.4 (9.2-30.7) months, respectively (p=0.83). There were 27 patients that received single agent chemotherapy and 41 patients that received combined regimen. There were 17 (42%) patients and 13 (48%) patients with partial response or stable disease in single and combined regimen. There were no differences in progression free survival and overall survival between single and multi agent chemotherapy. Conclusions: In this largest single institution study, second-line chemotherapy regimens for gallbladder cancer provided benefit in select patients and there is an urgent need to develop more active therapeutic regimens.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17019-e17019
Author(s):  
Patrik Palacka ◽  
Jana Katolicka ◽  
Tana Albertova ◽  
Katarina Rejlekova ◽  
Jana Obertova ◽  
...  

e17019 Background: Based on our previous study, the systemic immune-inflammation index (SII) is a prognostic factor in patients with metastatic urothelial cancer (MUC) treated with platinum-based first-line chemotherapy. The objective of this retrospective analysis was to explore prognostic value of the SII at baseline of second-line chemotherapy with vinflunine in MUC population. Methods: We evaluated 70 consecutive MUC (53 bladder, 21 upper tract) patients (54 men) treated with second-line chemotherapy with vinflunine at four oncological departments since 2010. ECOG performance status (PS) ≤ 1 had 44 patients (pts.), haemoglobin < 10 g/dL was present in 25 pts. and liver involvement in 18 pts. SII was based on platelets (P), neutrophils (N) and lymphocytes (L) counts defined as PxN/L. This study population was dichotomized by median into low SII and high SII groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared with logrank test. Results: At median follow-up of 9.0 months (1-29 months), 68 pts. experienced disease progression and 62 died. Pts. with low SII at baseline had significantly better PFS and OS opposite to those with high SII (HR = 0.61, 95% CI 0.37-1.00, p = 0.0318 for PFS, HR = 0.60, 95% CI 0.36-1.00, p = 0.0312 for OS, respectively). In addition to the prognostic factors by Bellmunt (ECOG PS ≥ 1, liver involvement, haemoglobin < 10 g/dL), we identified peritoneal metastases as a factor associated with significantly worse survival (HR = 0.28, 95% CI 0.11-0.72, p < 0.00001 for PFS, HR = 0.30, 95% CI 0.12-0.75, p < 0.00001 for OS, respectively). Conclusions: The SII at baseline of treatment with second-line vinflunine represents a prognostic factor for pts. with MUC. Based on SII, pts. could be stratified into clinical trials in future. MUC pts. with high SII might be candidates for a different treatment approach. Key Words: Metastatic Urothelial Carcinoma. Systemic Immune-Inflammation Index. Vinflunine. Progression-Free Survival. Overall Survival.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15648-e15648
Author(s):  
Y. Nakai ◽  
H. Isayama ◽  
T. Sasaki ◽  
N. Sasahira ◽  
K. Hirano ◽  
...  

e15648 Background: S-1 was reported to be active against gemcitabine (Gem)-refractory pancreatic cancer (PaC) in Japan and was introduced in February 2005 in our institution. The aim of this study was to elucidate the impact of S-1 on prognosis of patients with Gem- refractory PaC. Methods: A total of 108 patients (pts) with advanced PaC who were treated with Gem and had disease progression (PD) at the University of Tokyo Hospital were analyzed. The introduction rates of second-line chemotherapy and the causes of introduction failure were assessed. Prognostic factors for residual survival (RS) for Gem-refractory PaC were analyzed by the Cox proportional hazard model. Results: Of 108 pts with Gem-refractory PaC, 47 pts (PreS-1 Group) had PD before February 2005, the time of S-1 introduction in our institution, and 61 pts (PostS-1 Group) after February 2005. There were no differences in baseline characteristics at PD for Gem between PreS-1 and PostS-1 Groups, except for metastasis to peritoneum more prevalent in PreS-1 Group (44.7% in PreS-1 Group and 23.0% in PostS-1 Group, p=0.023). The introduction rate of second-line chemotherapy increased from 12.8% in PreS-1 Group to 45.9% in PostS-1 Group. Second-line chemotherapy was administered in 34 pts, 29 by S-1, 4 by 5-FU-based chemoradiation, and 1 by 5-FU. The causes of introduction failure of second line chemotherapy were poor PS in 64.9%, patients’ refusal in 16.2%, infection in 2.7%, adverse effects of Gem in 1.4% and jaundice in 1.4%. RR, PFS, and OS for second-line S-1 were 17.2%, 2.5 Mo, and 7.8 Mo, respectively. PFS for Gem was not prognostic of PFS for S-1 (2.5 Mo both in pts with PFS >6Mo and in pts with PFS <6Mo for Gem). RS after PD for Gem was prolonged from 3.1 Mo in PreS-1 Group to 6.5 Mo in PostS-1 Group (p<0.001). The Cox hazard model revealed PreS-1 Group (HR2.42, p=0.001) in addition to male gender (HR1.83, p=0.019), poor PS (HR3.52, p<0.001), liver metastasis (HR2.36, p=0.037), elevated LDH (per 100U/L increase) (HR 1.30, p=0.046), elevated CRP (HR 1.14, p=0.023) at PD for Gem as poor prognostic factors of RS for Gem-refractory PaC. Conclusions: Introduction of S-1 might lead to improvement of prognosis in patients with Gem-refractory PaC. No significant financial relationships to disclose.


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