Prognostic factors in glioblastoma multiforme

Abstract Objective: To study if the prognosis variables such as age, the Karnofsky Performance Status (KPS), extension of tumor removal by surgery, radiotherapy and tumor volume influenced the survival of patients with glioblastoma multiforme (GBM). Method: Retrospective analysis of GBM patients operated at Hospital dos Servidores do Estado between 1998 and 2008. Results: We could observe that age, the KPS and radiotherapy influenced the survival. The other variables did not have any prognosis implications. Conclusions: Despite many researches and many improvements regarding the diagnosis and the surgical techniques, the survival of patients with GBM has not changed in the last 30 years and is a therapeutic challenge. The surgical resection followed by radiotherapy is the standard treatment for patients with GBM. The importance of each variable in the patient's prognosis is still to be established in the multivariate analyzes.

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Glioblastoma Multiforme

JBNC - JORNAL BRASILEIRO DE NEUROCIRURGIA ◽

10.22290/jbnc.v24i1.1481 ◽

2018 ◽

Vol 24 (1) ◽

pp. 21-26

Author(s):

Leonardo Welling ◽

José Carlos Lynch ◽

Celestino Pereira ◽

Ricardo Andrade ◽

Fabiana Polycarpo Hidalgo ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Tumor Volume ◽

Standard Treatment ◽

Performance Status ◽

Surgical Techniques ◽

Surgical Removal ◽

Central Nervous System Tumor ◽

Tumor Group ◽

System Tumor ◽

Prognostic Implications

Objectives: Glioblastoma multiforme (GBM) has the highest malignancy grade in the astrocitic tumor group besides being the most common central nervous system tumor in adults. This paper aims to evaluate if the following factors: age, Karnofski Performance Status (KPS), extension of surgical removal, radiotherapy (RT), tumor volume and symptoms duration influenced the survival. Methods: We performed a retrospective analysis of GBM operated on at Hospital dos Servidores do Estado between 1986 and 2008. Results: We could observe that age, KPS and radiotherapy influenced the survival of patients. The other variables studied didnot have any prognostic implications. Conclusions: Despite many researches and several improvements regarding diagnosis and surgical techniques, the survivalof patients presenting with GBM could not be changed in the last 30 years. Surgical resection followed by RT is the standard treatment for patients with GBM. The importance of each prognostic factor is still to be established in a multivariate analysis.

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Glioblastoma Multiforme: an Advanced Analysis of 153 Patients and Review of the Literature

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery ◽

10.1055/s-0037-1603199 ◽

2017 ◽

Vol 36 (02) ◽

pp. 080-090 ◽

Cited By ~ 1

Author(s):

Mohammad Nikdad ◽

Farshid Farhan ◽

Milad Shafizadeh ◽

Atefeh Mirmohseni ◽

Mohsen Afarideh ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Local Recurrence ◽

Karnofsky Performance Status ◽

Performance Status ◽

Tertiary Care ◽

Cox Proportional Hazards ◽

Recurrence Rates ◽

Operative Method ◽

Factors Associated ◽

Advanced Analysis

Objective Glioblastoma multiforme (GBM) is an aggressive primary tumor with frequent recurrences that leaves patients with a short survival time and a low quality of life. The aim of this study was to review the prognostic factors in patients with glioblastoma multiforme. Material and Methods The focus of this retrospective study was a group of 153 patients with supratentorial GBM tumors, who were admitted to a tertiary-care referral academic center from 2005 to 2013. The factors associated with survival and local recurrence were assessed using the hazard ratio (HR) function of Cox proportional hazards regression and neural network analysis. Results Out of the 153 patients, 99 (64.7%) were male. The average age of the patients was 55.69 ± 15.10 years. The median overall survival (OS) and progression-free survival (PFS) rates were 14.0 and 7.10 months respectively. In the multivariate analysis, age (HR = 2.939, p < 0.001), operative method (HR = 7.416, p < 0.001), temozolomide (TMZ, HR = 11.723, p < 0.001), lomustine (CCNU, HR = 8.139, p < 0.001), occipital lobe involvement (HR = 3.088, p < 0.001) and Karnofsky Performance Status (KPS, HR = 4.831, p < 0.001) scores were shown to be significantly associated with a higher OS rate. Furthermore, higher KPS (HR = 7.292, p < 0.001) readings, the operative method (HR = 0.493, p = 0.005), the use of CCNU (HR = 2.047, p = 0.003) and resection versus chemotherapy (HR = 0.171, p < 0.001) were the significant factors associated with the local recurrence of the tumor. Conclusion Our findings suggest that the use of CCNU and TMZ, the operative method and higher KPS readings are associated with both higher survival and lower local recurrence rates.

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Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases

Neurosurgery ◽

10.1093/neuros/nyx380 ◽

2017 ◽

Vol 83 (2) ◽

pp. 237-244 ◽

Cited By ~ 7

Author(s):

Brian R Hirshman ◽

Bayard R Wilson ◽

Mir Amaan Ali ◽

Alexander J Schupper ◽

James A Proudfoot ◽

...

Keyword(s):

Prognostic Value ◽

Tumor Volume ◽

Karnofsky Performance Status ◽

Performance Status ◽

Intracranial Tumor ◽

Assessment Model ◽

Prognostic Assessment ◽

Prognostic Accuracy ◽

Graded Prognostic Assessment ◽

Independent Cohort

Abstract BACKGROUND The diagnosis-specific graded prognostic assessment scale (ds-GPA) for patients with melanoma brain metastasis (BM) utilizes only 2 key prognostic variables: Karnofsky performance status and the number of intracranial metastases. We wished to determine whether inclusion of cumulative intracranial tumor volume (CITV) into the ds-GPA model for melanoma augmented its prognostic value. OBJECTIVE To determine whether or not CITV augments the ds-GPA prognostic scale for melanoma. METHODS We analyzed the survival pattern of 344 melanoma patients with BM treated with stereotactic radiosurgery (SRS) at separate institutions and validated our findings in an independent cohort of 201 patients. The prognostic value of ds-GPA for melanoma was quantitatively compared with and without the addition of CITV using the net reclassification index (NRI > 0) and integrated discrimination improvement (IDI) metrics. RESULTS The incorporation of CITV into the melanoma-specific ds-GPA model enhanced its prognostic accuracy. Addition of CITV to the ds-GPA model significantly improved its prognostic value, with NRI > 0 of 0.366 (95% CI: 0.125-0.607, P = .002) and IDI of 0.024 (95% CI: 0.008-0.040, P = .004). We validated these findings that CITV improves the prognostic utility of melanoma ds-GPA in an independent cohort of 201 melanoma cohort. CONCLUSION The prognostic value of the ds-GPA scale for melanoma BM is enhanced by the incorporation of CITV.

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Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.7.1368 ◽

1993 ◽

Vol 11 (7) ◽

pp. 1368-1375 ◽

Cited By ~ 201

Author(s):

L M Minasian ◽

R J Motzer ◽

L Gluck ◽

M Mazumdar ◽

V Vlamis ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Prognostic Factors ◽

Cell Carcinoma ◽

Renal Cell ◽

Karnofsky Performance Status ◽

Performance Status ◽

Interferon Alfa ◽

Advanced Renal Cell Carcinoma ◽

Survival Duration

PURPOSE Three trials were conducted to define the efficacy and toxicity of interferon alfa-2a in the treatment of metastatic renal cell cancer. Univariate and multivariate analyses were performed to identify prognostic factors for survival. PATIENTS AND METHODS Prospectively, 159 patients were treated with interferon alfa-2a. In the first trial, 42 patients received 50 x 10(6) U/m2 intramuscularly three times per week. In the second trial, 64 patients received gradually escalating doses of interferon alfa-2a from 3 to 36 x 10(6) U subcutaneously administered daily. The third trial was randomized; 25 patients received daily interferon alfa-2a alone and 28 were treated with daily interferon alfa-2a and 0.15 mg/kg vinblastine every 3 weeks. RESULTS The overall response proportion was 10% (two complete and 14 partial responses). The median response duration was 12.2 months. The median survival duration was 11.4 months, with 3% of patients alive at 5 or more years. A univariate statistical analysis showed that a Karnofsky performance status > or = 80, prior nephrectomy, and interval from diagnosis to treatment of longer than 365 days were significant prognostic factors for survival. In a multivariate analysis, only prior nephrectomy and Karnofsky performance status > or = 80 were shown to be independent predictors of survival. CONCLUSION Interferon alfa-2a had minimal antitumor activity in patients with advanced renal cell carcinoma and long-term survival was achieved in a small proportion of patients. The need for continued investigation and the identification of more effective therapy for advanced renal cell carcinoma is evident from the poor overall survival rate observed in these 159 patients. The investigation of new agents and of interferon alfa-2a in combination with other agents remains a priority.

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Treatment of Glioblastoma Multiforme in Elderly Patients. Clinico-therapeutic Remarks in 22 Patients Older than 80 Years

Tumori Journal ◽

10.1177/030089160609200203 ◽

2006 ◽

Vol 92 (2) ◽

pp. 98-103 ◽

Cited By ~ 26

Author(s):

Manolo Piccirilli ◽

Simona Bistazzoni ◽

Franco Maria Gagliardi ◽

Alessandro Landi ◽

Antonio Santoro ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Elderly Patients ◽

Karnofsky Performance Status ◽

Performance Status ◽

Multimodality Treatment ◽

Good Health ◽

Rank Test ◽

Significant Prognostic Factor ◽

Log Rank Test ◽

Common Opinion

We report our remarks on 22 patients, 80 years of age and older, who were treated for glioblastoma multiforme. The 16 patients who underwent a multimodality treatment (surgery + radiotherapy + chemotherapy) had an average survival of 16.7 months versus the 5.8 months of the 8 patients treated with biopsy followed by radiotherapy and/or chemotherapy (log-rank test, P <0.001). Moreover, we point out the importance of MGMT hypermethylation as a significant prognostic factor: the 9 patients with nonmethylated MGMT had a mean survival of 7.7 months vs 17.9 months of the 13 patients with the MGMT promoter methylated (log-rank test, P = 0.0006). Several studies have pointed out age as an important negative factor for the outcome of elderly patients affected by glioblastoma multiforme. Elderly patients with a diagnosis of glioblastoma multiforme are thus generally excluded from clinical trials of treatment for the neoplasm, because it is a common opinion that the prognosis for such patients is particularly poor. On the contrary, according to our clinical and surgical experience, we firmly believe that patients older than 80 years with a histologically proven diagnosis of glioblastoma multiforme and in good health conditions (Karnofsky performance status >60) should be treated in the same way as younger patients.

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Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review

Neurosurgery ◽

10.1093/neuros/nyx346 ◽

2017 ◽

Vol 83 (1) ◽

pp. 128-136 ◽

Cited By ~ 2

Author(s):

E Emily Bennett ◽

Michael A Vogelbaum ◽

Gene H Barnett ◽

Lilyana Angelov ◽

Samuel Chao ◽

...

Keyword(s):

Prognostic Factors ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Karnofsky Performance Status ◽

Systemic Disease ◽

Performance Status ◽

Early Death ◽

Tumor Type ◽

Prognostic Groups ◽

Prior Surgery

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival. OBJECTIVE To evaluate prognostic factors, which may predict early death (within 90 d) after SRS. METHODS A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices. RESULTS Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatment, total tumor volume, prior surgery, and interval from primary to BM were independent prognostic factors for 90-d mortality. The first 4 factors were also independent predictors in patients treated with salvage SRS. Based on these factors, an index was defined for each group that categorized patients into 3 and 2 prognostic groups, respectively. Ninety-day mortality was 5% to 7% in the most favorable cohort and 36% to 39% in the least favorable. CONCLUSION Indices based on readily available patient, clinical, and treatment factors that are highly predictive of early death in patients treated with upfront or salvage SRS can be calculated and used to define well-separated prognostic groups.

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Prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF)-targeted agents: Results from a large multicenter study

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5041 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5041-5041

Author(s):

D. Y. Heng ◽

W. Xie ◽

M. M. Regan ◽

T. Cheng ◽

S. North ◽

...

Keyword(s):

Prognostic Factors ◽

Karnofsky Performance Status ◽

Performance Status ◽

Large Population ◽

Cox Proportional Hazards Model ◽

Parameter Estimates ◽

Targeted Agents ◽

Anti Vegf ◽

Risk Categories ◽

Metastatic Rcc

5041 Background: Prognostic factors (PF) for OS have yet to be fully defined for patients with metastatic RCC in the era of VEGF-targeted therapy. This study identifies PFs in this population and updated survival and validation results are presented. Methods: Baseline characteristics and outcomes on anti-VEGF-naïve metastatic RCC patients were collected from three US and four Canadian centers. Using a Cox proportional hazards model, 3 risk categories for predicting survival were identified on the basis of 6 pretreatment clinical features. Results: Six-hundred forty-five patients were included. The median (m) OS was 22 months (95% CI: 20.0–24.8) with a median follow-up of 25 months. Patients were treated with sunitinib (n = 396), sorafenib (n = 200) or bevacizumab (n = 49); 33% had prior immunotherapy. Four of the five PFs previously identified by MSKCC were independent predictors of short survival, including hemoglobin below the lower limit of normal (LLN) (p < 0.0001), corrected calcium above the upper limit of normal (ULN) (p = 0.0006), Karnofsky performance status <80% (p < 0.0001) and time from initial diagnosis to initiation of therapy ULN (pULN (p = 0.012) were independent adverse PFs. Patients were assigned one point for each poor PF and were segregated into three risk categories: favorable-risk (0 PFs, n = 133) median OS (mOS) 37.0 months; intermediate-risk (1 - 2 PFs, n = 292) mOS 28.5 months; and poor-risk (3–6 PFs, n = 139) mOS 9.4 months (log rank p < 0.0001). This model produced a c-index of 0.74 and the bootstrap procedure confirmed good internal validity. The discriminatory ability of the model and its parameter estimates were not affected after adjusting for prior use of immunotherapy or the type of anti-VEGF drug used. Conclusions: These data validate components of the MSKCC model with the addition of platelet and neutrophil counts. This model derived from a large population can be incorporated into patient care and clinical trials of VEGF-targeted agents. [Table: see text]

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Clinical predictors of second-line chemotherapy (ChT) benefit in pancreatic cancer (PC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15733 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15733-e15733

Author(s):

Ilya Pokataev ◽

Igor Bazin ◽

Mikhail Fedyanin ◽

Alexey Tryakin ◽

Anna Popova ◽

...

Keyword(s):

Prognostic Factors ◽

Disease Progression ◽

Proportional Hazards Model ◽

Karnofsky Performance Status ◽

Performance Status ◽

Prognostic Significance ◽

Cox Proportional Hazards Model ◽

Second Line ◽

Inclusion Criteria ◽

Prognosis Score

e15733 Background: Second line ChT is shown to improve outcome in selected patients with PC; however there are no approved models predicting its benefit. This retrospective study was aimed to evaluate prognostic factors in patients with PC who had disease progression following 1st line ChT and their value in prediction of 2nd line ChT benefit. Methods: Records of PC patients treated in N.N. Blokhin Russian Cancer Research Center since 2000 to 2015 were analyzed. Inclusion criteria for this retrospective analysis were: morphologically confirmed PC, disease progression after 1st line ChT or adjuvant / induction ChT with ChT-free interval <6 months. The most common clinical factors were evaluated for prognostic significance in the Cox proportional hazards model with overall survival (OS) as the end-point. OS was calculated from the date of progression following previous ChT. Cutoff values for quantitative variables were determined using ROC curve analyses. Results: Records of 172 patients matched the inclusion criteria. Second line ChT was administered in 110 (64%) patients (47% of them received gemcitabine- and/or platinum-based doublets). The Cox multivariate analysis identified two independent prognostic factors: Karnofsky performance status (KPS) ≤70% and neutrophil-to-lymphocyte ratio (NLR) >5 at the time of disease progression after 1st line ChT (Table). Administration of 2nd line ChT improved outcome of patients with favorable prognosis (score ≤1): median OS increased from 1.7 to 5.5 months in groups without (n=23) and with (n=90) ChT, respectively (p=0.02). In patients with poor prognosis (score>1) there were no benefit by administration of 2nd line ChT: medians OS were 2.3 and 1.7 months in groups with (n=20) and without (n=39) ChT, respectively (p=0.23). Conclusions: This novel prognostic model can potentially predict 2nd line ChT benefit in patients with PC, however it needs to be validated in further trials. [Table: see text]

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EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps2072 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS2072-TPS2072 ◽

Cited By ~ 2

Author(s):

Patrick Roth ◽

Jaap C. Reijneveld ◽

Thierry Gorlia ◽

Frederic Dhermain ◽

Filip Yves Francine Leon De Vos ◽

...

Keyword(s):

Standard Treatment ◽

Karnofsky Performance Status ◽

Performance Status ◽

Primary Objective ◽

Recurrent Glioblastoma ◽

Phase Iii ◽

Newly Diagnosed ◽

Open Label ◽

Phase Iii Trial ◽

Newly Diagnosed Glioblastoma

TPS2072 Background: The standard treatment for patients with newly diagnosed glioblastoma comprises maximum safe surgery, radiotherapy (RT), and concomitant and up to six cycles of maintenance temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). Despite this intense therapy, the prognosis remains poor and there is an urgent need to develop new therapeutic options. Marizomib is a novel, irreversible and brain-penetrant pan-proteasome inhibitor. Following its successful assessment in phase I trials in patients with newly diagnosed as well as recurrent glioblastoma, marizomib is now being investigated in a phase III trial. Methods: EORTC 1709/CCTG CE.8 is a multicenter, randomized, controlled, open label phase III superiority trial. Eligibility criteria include histologically confirmed newly diagnosed glioblastoma and a performance status ≥70. Approximately a total of 750 patients will be enrolled and randomized 1:1. Stratification factors include institution, age, Karnofsky performance status and extent of surgery. The primary objective of this study is to compare overall survival in patients receiving marizomib in addition to standard of care (TMZ/RT→TMZ) with patients receiving standard treatment only. The testing strategy specifies the determination of this objective in both the intent-to-treat population and the subgroup of patients with tumors harboring an unmethylated MGMT promoter. Secondary endpoints include progression-free survival, safety, neurocognitive function and quality of life. The study is accompanied by a translational research program. The study will be opened at 50 EORTC sites in Europe and done as an intergroup collaboration with the Canadian Cancer Trials Group (CCTG) with 25 sites in Canada and additional sites in the US. Patient enrolment started in June 2018 and as of January 29, 2019, a total of 85 patients have been randomized. An update on the enrolment status will be provided at the ASCO conference. Clinical trial information: NCT03345095.

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Abbreviated Course of Radiation Therapy in Older Patients With Glioblastoma Multiforme: A Prospective Randomized Clinical Trial

Journal of Clinical Oncology ◽

10.1200/jco.2004.06.082 ◽

2004 ◽

Vol 22 (9) ◽

pp. 1583-1588 ◽

Cited By ~ 502

Author(s):

W. Roa ◽

P.M.A. Brasher ◽

G. Bauman ◽

M. Anthes ◽

E. Bruera ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Glioblastoma Multiforme ◽

Older Patients ◽

Treatment Time ◽

Karnofsky Performance Status ◽

Performance Status ◽

Wilcoxon Test ◽

Rank Test ◽

Survival Times

Purpose To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). Patients and Methods One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). Results All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P = .57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, −13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P = .63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (χ2 test, P = .02). Conclusion There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

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