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

2004 ◽  
Vol 22 (9) ◽  
pp. 1583-1588 ◽  
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.

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

2006 ◽  
Vol 92 (2) ◽  
pp. 98-103 ◽  
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.

N-cadherin, E-cadherin, ERCC1, and c-kit expression in small cell lung cancer (SCLC) and potential for new therapeutic targets

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22157-e22157
Author(s):  
M. Batus ◽  
R. Myint ◽  
J. Coon ◽  
S. Basu ◽  
K. Kaiser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Molecular Markers ◽  
Performance Status ◽  
Prognostic Significance ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Clinical Activity ◽  
Log Rank Test ◽  
Treatment Type ◽  
E Cadherin

e22157 Background: Minimal advances have been made in the treatment of SCLC. Molecular markers may allow us to better stratify patients (pts) for new treatment options and drug combinations. The objective of our study was to determine the frequency and potential prognostic significance of N-cadherin (N-cad), E-cadherin (E-cad), ERCC1, and c-kit (CD117) expression in SCLC. Methods: Tissue from 132 pts with SCLC was retrospectively stained for N-cad, E-cad, ERCC1, and c-kit. Frequency of expression (% of tumor cells staining positive) was measured on a scale of 0–4 (freq 0=no expression (<1%), freq 1=1–10%, freq 2=11–35%, freq 3=36–70%, freq 4=71–100%). Charts were reviewed for stage, performance status, date of diagnosis/death, survival, and treatment (type, dates, response). The frequency of molecular markers was correlated with clinical data and overall survival. Results: Age range 42 to 97 years, 65 male:67 female, and 64 had limited and 68 had extensive stage. Of the 132 pts, 75% had tumors that expressed (frequency ≥ 1) N-cad, 58% E-cad, 70% ERCC1, and 55% c-kit. Comparing tumor marker expression with survival using either the Log-Rank Test or the Wilcoxon Test, there was no significant association for N-cad, E-cad, or ERCC1. However, tumors that expressed c-kit with frequency ≥ 3 had a trend toward superior survival compared with frequency < 3. Median survival for c-kit frequency ≥ 3 was 496 days compared to 312 days for frequency < 3 (p = 0.09, Log-Rank Test). Conclusions: In our retrospective study of 132 SCLC pts, we found that all 4 markers were expressed in greater than 50% of specimens, and that higher c-kit expression was associated with marginally significant increase in overall survival. Though previous experience with imatinib alone or with chemotherapy showed limited clinical activity in unselected SCLC pts, given preclinical synergy with cisplatin, it seems reasonable to consider combination therapy with cisplatin/etoposide and imatinib in pts selected for high c-kit expression. [Table: see text] No significant financial relationships to disclose.

Brain metastases in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 326-326
Author(s):  
H. Alharbi ◽  
T. K. Choueiri ◽  
C. K. Kollmannsberger ◽  
S. North ◽  
M. J. MacKenzie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Time ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Local Treatment ◽  
Multivariable Analysis ◽  
First Line ◽  
The Brain

326 Background: Patients with brain metastases from advanced RCC treated in the targeted therapy era are not well characterized. Methods: Data from patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium from 6 centers. Results: One hundred six out of 705 (15%) patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti-VEGF therapy and the rest developed metastases during follow-up. Of the patients with brain metastases, 6%, 68%, and 26% were in the favorable, intermediate and poor prognosis groups, respectively, per the Heng et al JCO 2009 criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 40% had a Karnofsky performance status (KPS) <80%, and 81% had symptoms of brain metastases. The median largest size and number of brain metastases was 1.8 cm (range 0.2–6.6) and 1 (range 1–20), respectively. Patients were treated with first-line sunitinib (n=77), sorafenib (n=23), bevacizumab (n=5), and temsirolimus (n=1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). The brain metastases of 59 patients were evaluable and based on the local treatment and/or targeted therapy achieved 7 (12%) complete responses, 23 (39%) partial responses, 14 (24%) patients with stable disease, and 15 (25%) patients with progressive disease in the brain metastases. Patients with more than 4 brain metastases vs. those with no more than 4 have an overall survival time from diagnosis of brain metastasis of 3.9 vs. 15.4 months (p=0.0051). Previous nephrectomy, sarcomatoid, and non-clear cell histology are not associated with development of brain metastases. On multivariable analysis, KPS<80% (p=0.0139), diagnosis to treatment with targeted therapy <1 year (p=0.0012), and higher number of brain metastases (p=0.0311) were associated with worse survival from diagnosis of brain metastases. Conclusions: In patients with brain metastases from RCC, KPS at start of therapy, diagnosis to treatment time and number of brain metastases may be prognostic factors for overall survival. [Table: see text]

Tandem Cycle High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Maintenance Interferon Alpha-2 (IF) with or without Thalidomide (Thal) Is Associated with High Complete and Very Good Partial Response Rates, Improved Progression-Free, and Overall Survival.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3089-3089
Author(s):  
George Somlo ◽  
Dajun Qian ◽  
Firoozeh Sahebi ◽  
Neil Martin Kogut ◽  
Roberto Rodriguez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Concomitant Administration ◽  
Entire Group ◽  
High Dose ◽  
Day Range ◽  
High Dose Melphalan ◽  
To Receive

Abstract Tandem cycle high-dose melphalan (Mel) followed by Mel +/− total body radiation therapy improves progression-free (PFS) and overall survival (OS) in comparison to single cycle Mel, but is associated with 3% treatment-related mortality (TRM). We tested a new tandem regimen (THDCT) followed by maintenance therapy in order to lower TRM, while enhancing efficacy. Between 5/94 and 8/04, 114 patients (pts) were enrolled on 2 sequential studies. First, pts received Mel 150 mg/m2 [cycle 1 (C1)], oral busulfan (bu 16 mg/kg; 46 pts), and cyclophosphamide 120 mg/kg (Cy; C2); the next cohort received the same THDCT but bu was given intravenously (i.v. 12.8 mg/kg; 68 pts). All pts were to receive maintenance IF 3 million units/m2 given subcutaneously, 3 times/week. Pts participating on the 2nd study were to receive thal together with IF provided that they were not in CR at 6 months post-THDCT. Peripheral blood progenitor cell mobilization consisted of G-CSF 10 microgram/kg to procure 4 x 106 CD34+ cells/kg without (first 46 pts) or with Cy 1.5 g/m2 (last 68 pts). Pts ≤65 years, with responsive or stable MM, with <40% marrow involvement, with a creatinine clearance of 70 cc/min and Karnofsky performance status of 70% were enrolled. Median age was 52 years (range: 29–65); 70% of pts were diagnosed with stage III MM, and 4 pts presented with plasma cell leukemia; 40% received prior radiation therapy. Pts received a median of 1(1–3) induction chemotherapy regimens; the median time from diagnosis to THDCT was 8 months (range: 2–73); 89% of pts received both C-s at a median of 76 days (range, 29–134). Among the first 46 pts (treated with oral bu) there were 7 cases of veno-occlusive disease (VOD): 3 were fatal, resulting in TRM of 7%. There were 8 cases of VOD in the 68 pt cohort treated with i.v. bu, one of whom died of multi-organ failure/sepsis (TRM:1.5%). Eighty nine percent of pts tolerated at least 1 million units/m2 of IF 2–3 times/week. Of pts receiving concomitant IF and thal (median dose of thal: 100 mg/day[range, 50–400]), only 7 pts tolerated both (median: 4 months; range: 1.6–18 months), 3 of whom converted to CR. At best response 44% pts were in CR and 12% achieved 90% reduction (very good partial remission (VGPR). For the entire group, 3-year PFS is 50% (95% CI, 40–59%) and OS is 71% (95%CI, 61–78%). Three-year PFS is 66% (95% CI 52–76%) vs. 29% (95% CI 16–42%) and OS is 87% (95% CI 76–93%) vs. 49% (95% CI 35–63%) favoring pts in CR and VGPR vs. all others. THDCT with Mel and i.v. bu /Cy and maintenance IF can be given safely, and may provide an alternative regimen to tandem Mel. Concomitant administration of IF and thal is not feasible. Thal should be used either in sequence or in lieu of IF as maintenance.

GliaSite Brachytherapy for Treatment of Recurrent Malignant Gliomas:A Retrospective Multi-institutional Analysis

Neurosurgery ◽  
2006 ◽  
Vol 58 (4) ◽  
pp. 701-709 ◽  
Author(s):  
Arash J. Gabayan ◽  
Sylvan B. Green ◽  
Abhay Sanan ◽  
Joseph Jenrette ◽  
Christopher Schultz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Karnofsky Performance Status ◽  
External Beam Radiotherapy ◽  
Performance Status ◽  
Malignant Gliomas ◽  
Balloon Catheter ◽  
Median Dose ◽  
Karnofsky Performance Status Score

Abstract OBJECTIVE: To review the cumulative experience of 10 institutions in treating recurrent malignant gliomas with the brachytherapy device, GliaSite Radiation Therapy System. METHODS: The patient population consisted of 95 patients with recurrent grade 3 or 4 gliomas, a median age of 51 years, and a median Karnofsky performance status score of 80. All patients had previously undergone resection and had received external beam radiotherapy as part of their initial treatment. After recurrence, each patient underwent maximal surgical debulking of their recurrent lesion and placement of an expandable balloon catheter (GliaSite) in the tumor cavity. The balloon was afterloaded with liquid 125I (Iotrex) to deliver a median dose of 60 Gy to an average depth of 1 cm with a median dose rate of 52.3 Gy/hr. Patients were carefully followed with serial magnetic resonance imaging and monthly examinations for tumor progression, side effects, and survival. RESULTS: The median survival for all patients, measured from date of GliaSite placement, was 36.3 weeks with an estimated 1 year survival of 31.1%. The median survival was 35.9 weeks for patients with an initial diagnosis of glioblastoma multiforme and 43.6 weeks for those with non- glioblastoma multiforme malignant gliomas. Analysis of the influence of various individual prognostic factors on patient survival demonstrated that only Karnofsky performance status significantly predicted for improved survival. There were three cases of pathologically documented radiation necrosis. CONCLUSION: Reirradiation of malignant gliomas with the GliaSite Radiation Therapy System after reresection seems to provide a modest survival benefit above what would be expected from surgery alone. This report not only confirms the initial results of the feasibility study but provides evidence that similar outcomes can be obtained outside of a clinical trial.

scholarly journals Preventing Discontinuation of Radiation Therapy: Predictive Factors to Improve Patient Selection for Palliative Treatment

2017 ◽  
Vol 13 (9) ◽  
pp. e782-e791 ◽  
Author(s):  
Lindsay L. Puckett ◽  
Eric Luitweiler ◽  
Louis Potters ◽  
Sewit Teckie
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Bone Metastasis ◽  
Brain Metastases ◽  
Patient Selection ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Factors Associated ◽  
Patients With Cancer ◽  
Selection For

Purpose: Approximately one third of patients with cancer require palliative radiation therapy (PRT), yet no guidelines exist for optimal patient selection. We have observed that many patients who begin PRT do not complete their prescribed treatment. Our study sought to identify factors associated with discontinuation of PRT, assess for a relationship with survival, and inform patient selection. Methods: We performed an institutional review board–approved retrospective analysis of patients with cancer treated in a multicenter radiation oncology department in 2014. Of 297 patients who began PRT, 60 discontinued and 237 completed treatment. Primary end points included discontinuation and overall survival. Results: Patient factors were analyzed for association with discontinuation of PRT and overall survival, respectively, using logistic regression and Cox proportional regression models. Factors associated with discontinuation were low Karnofsky performance status (KPS) score, high number of fractions prescribed, and treatment site other than bone metastasis. The odds of discontinuing PRT decreased by approximately 52% for every 10-point increase in KPS score (odds ratio, 0.48; 95% CI, 0.36 to 0.63; P < .001). Factors associated with shorter survival included discontinuation of PRT, low KPS score, community practice location, multiple comorbidities, and treatment of brain metastases. Patients who discontinued treatment were more likely to die than patients who completed treatment, independent of other factors (hazard ratio, 3.67; 95% CI, 2.41 to 5.61; P < .001). Conclusion: Patients with low KPS scores, long treatment courses, and those treated to sites other than bone metastasis were significantly more likely to discontinue treatment. Discontinuation was predictive for poor survival. Pretreatment evaluation of KPS, comorbidities, and brain metastases can help guide appropriate patient selection for PRT.

Gamma Knife Stereotactic Radiosurgery for Patients with Glioblastoma Multiforme

Neurosurgery ◽  
2002 ◽  
Vol 50 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Emmanuel C. Nwokedi ◽  
Steven J. DiBiase ◽  
Salma Jabbour ◽  
Joseph Herman ◽  
Pradip Amin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Glioblastoma Multiforme ◽  
Stereotactic Radiosurgery ◽  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Cox Regression Analysis ◽  
Group 2 ◽  
Group 1

ABSTRACT OBJECTIVE Stereotactic radiosurgery (SRS) has become an effective therapeutic modality for the treatment of patients with glioblastoma multiforme (GBM). This retrospective review evaluates the impact of SRS delivered on a gamma knife (GK) unit as an adjuvant therapy in the management of patients with GBM. METHODS Between August 1993 and December 1998, 82 patients with pathologically confirmed GBM received external beam radiotherapy (EBRT) at the University of Maryland Medical Center. Of these 82 patients, 64 with a minimum follow-up duration of at least 1 month are the focus of this analysis. Of the 64 assessable patients, 33 patients were treated with EBRT alone (Group 1), and 31 patients received both EBRT plus a GK-SRS boost (Group 2). GK-SRS was administered to most patients within 6 weeks of the completion of EBRT. The median EBRT dose was 59.7 Gy (range, 28–70.2 Gy), and the median GK-SRS dose to the prescription volume was 17.1 Gy (range, 10–28 Gy). The median age of the study population was 50.4 years, and the median pretreatment Karnofsky performance status was 80. Patient-, tumor-, and treatment-related variables were analyzed by Cox regression analysis, and survival curves were generated by the Kaplan-Meier product limit. RESULTS Median overall survival for the entire cohort was 16 months, and the actuarial survival rate at 1, 2, and 3 years were 67, 40, and 26%, respectively. When comparing age, Karnofsky performance status, extent of resection, and tumor volume, no statistical differences where discovered between Group 1 versus Group 2. When comparing the overall survival of Group 1 versus Group 2, the median survival was 13 months versus 25 months, respectively (P = 0.034). Age, Karnofsky performance status, and the addition of GK-SRS were all found to be significant predictors of overall survival via Cox regression analysis. No acute Grade 3 or Grade 4 toxicity was encountered. CONCLUSION The addition of a GK-SRS boost in conjunction with surgery and EBRT significantly improved the overall survival time in this retrospective series of patients with GBM. A prospective, randomized validation of the benefit of SRS awaits the results of the recently completed Radiation Therapy Oncology Group's trial RTOG 93-05.

Phase III Study Comparing Three Cycles of Infusional Carmustine and Cisplatin Followed by Radiation Therapy With Radiation Therapy and Concurrent Carmustine in Patients With Newly Diagnosed Supratentorial Glioblastoma Multiforme: Eastern Cooperative Oncology Group Trial 2394

2003 ◽  
Vol 21 (8) ◽  
pp. 1485-1491 ◽  
Author(s):  
Stuart A. Grossman ◽  
Anne O’Neill ◽  
Margaret Grunnet ◽  
Minesh Mehta ◽  
James L. Pearlman ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Oncology Group ◽  
Ambulatory Treatment

Purpose: This phase III Eastern Cooperative Oncology Group-Southwest Oncology Group intergroup study was conducted to determine whether three 72-hour infusions of carmustine (BiCNU) and cisplatin administered monthly before external-beam radiotherapy would improve the survival of patients with newly diagnosed glioblastoma multiforme. The control arm consisted of radiation with standard adjuvant BiCNU. Patients and Methods: A total of 223 patients were accrued from 1996 to 1999. Of these, 219 patients were eligible; 109 were randomly assigned to the experimental arm, and 110 were randomly assigned to the control arm. Randomization was stratified by age, performance status, and extent of resection. Results: The median age of the patients was 55 years; 55% were male, 93% were white, 26% had a biopsy only, and 84% were ambulatory. Treatment arms were well balanced with respect to baseline characteristics. Median follow-up time of the 15 patients still alive at the time of analysis was 3.3 years (range, 2 to 5 years). Median survival times for the standard and experimental arms were 11.2 and 11.0 months (P = .33, two-sided log-rank test), and survival at 1 year was 45% versus 44%, respectively. Fifty-six percent of patients received all three cycles of BiCNU/cisplatin, 12% received two cycles, and 31% received only one cycle. Toxicity was primarily hematologic and was more common in the experimental arm (P < .01). Conclusion: This study demonstrates that 72-hour infusions of BiCNU and cisplatin followed by radiation do not improve median survival, survival at 1 year, or time to progression. Furthermore, this treatment requires more time in the hospital and is associated with more serious toxicities than standard therapy.

Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83-02.

1993 ◽  
Vol 11 (5) ◽  
pp. 857-862 ◽  
Author(s):  
W J Curran ◽  
C B Scott ◽  
A S Weinstein ◽  
L A Martin ◽  
J S Nelson ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Malignant Glioma ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Radiation Therapy Oncology Group ◽  
Survival Rates ◽  
Optic Chiasm ◽  
Oncology Group ◽  
Survival Times ◽  
Hyperfractionated Radiotherapy

PURPOSE The purpose is twofold: (1) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy (RT) and carmustine (BCNU) who may have been eligible for a stereotactic radiosurgery (SRS) boost; and (2) to compare survival of such patients with that of those considered SRS-ineligible. PATIENTS AND METHODS From January 1983 to July 1989, 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group (RTOG) 83-02, a randomized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy. The SRS criteria used in a single-institution trial were applied to these patients; they are: Karnofsky performance status (KPS) of greater than 60; well-circumscribed tumor less than 4.0 cm; no subependymal spread; and a location not adjacent to brainstem or optic chiasm. RESULTS Eighty-nine patients (11.9%) were identified as potentially SRS-eligible. The median survival times (MST) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40% versus 27%, respectively (P = .047). The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29%, respectively, and were not statistically inferior to the survival of the SRS-eligible group (P = .21). Multivariate analysis revealed age, KPS, and histopathology to be strongly predictive of survival, and SRS eligibility was also significantly predictive (P = .047). CONCLUSION SRS-eligible patients enrolled on RTOG 83-02 had survival superior to that of the SRS-ineligible group, and this advantage is mainly due to the selection of a subgroup with a high minimum KPS.

METIS: A phase 3 study of radiosurgery with TTFields for 1-10 brain metastases from NSCLC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9106-TPS9106
Author(s):  
Minesh P. Mehta ◽  
Vinai Gondi ◽  
Paul D. Brown
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Karnofsky Performance Status ◽  
Systemic Disease ◽  
Performance Status ◽  
Rank Test ◽  
In Vivo Models ◽  
To Receive ◽  
The Brain

TPS9106 Background: Tumor Treating Fields (TTFields) are non-invasive regional anti-mitotic treatment modality, based on low intensity alternating electric fields. Efficacy of TTFields in non-small cell lung cancer (NSCLC) has been demonstrated in multiple in vitro and in vivo models, and in a phase I/II clinical study. TTFields treatment to the brain was shown to be safe and to extend overall survival in newly-diagnosed glioblastoma patients. Methods: 270 patients with 1-10 brain metastases (BM) from NSCLC will be randomized in a ratio of 1:1 to receive stereotactic radio surgery (SRS) followed by either TTFields or supportive care alone. Patients are followed-up every two months until 2nd cerebral progression. Patients in the control arm may cross over to receive TTFields at the time of 2st cerebral progression. Objectives: To test the efficacy, safety and neurocognitive outcomes of TTFields in this patient population. Endpoints: Time to 1st cerebral progression based on the RANO-BM Criteria or neurological death (primary); time to neurocognitive failure based on the following tests: HVLT, COWAT and TMT; overall survival; radiological response rate; quality of life; adverse events severity and frequency (secondary). Main eligibility criteria: Karnofsky performance status (KPS) of 70 or above, 1 inoperable or 2-10 brain lesions amenable to SRS, optimal standard therapy for the extracranial disease, no brain-directed therapy, no signs of significantly increased intracranial pressure, no electronic implantable devices in the brain. Treatment: Continuous TTFields at 150 kHz for at least 18 hours per day will be applied to the brain within 7 days of SRS. The treatment system is a portable medical device allowing normal daily activities. The device delivers TTFields to the brain using 4 Transducer Arrays, which may be covered by a wig or a hat for cosmetic reasons. Patients will receive the best standard of care for their systemic disease. Statistical Considerations: This is a prospective, randomized, multicenter study for 270 patients. The sample size was calculated using a log-rank test (based on Lakatos 1988 and 2002) and has 80% power at a two sided alpha of 0.05 to detect a hazard ratio of 0.57. Clinical trial information: NCT02831959.

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