A phase II study of radiosurgery and temozolomide for patients with one to four brain metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2048-2048 ◽  
Author(s):  
J. B. Fiveash ◽  
S. M. Sawrie ◽  
B. L. Guthrie ◽  
S. A. Spencer ◽  
R. F. Meredith ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Median Number ◽  
Serious Adverse Events ◽  
Whole Brain Radiation ◽  
Brain Failure ◽  
Actuarial Risk ◽  
One Year ◽  
Distant Brain Failure

2048 Background: To determine if temozolomide reduces the risk of distant brain failure (DBF, metachronous brain metastases) in patients with 1–4 brain metastases treated with radiosurgery without whole brain radiation therapy. Methods: Twenty-five patients with newly diagnosed brain metastases were enrolled in a single institution phase II trial of radiosurgery (15–24 Gy) and adjuvant temozolomide. Temozolomide was started within 14 days of radiosurgery and was administered 150–200 mg/m2 p.o. q day x 5 days in 28 day cycles. Temozolomide was continued for a total of 12 cycles unless the patient developed DBF, unacceptable toxicity, or systemic progression requiring other therapy. If more than 4 metastases were identified on the MRI performed on the day of radiosurgery, then the patient could still be treated on the clinical trial if all tumors could be treated with radiosurgery. In addition to clinical and radiographic follow-up, QOL was assessed utilizing the FACT-Br questionnaire. Results: Twenty-five patients were enrolled 2002–2005; three were not evaluable for determining DBF. Of the remaining twenty-two patients, tumor types included NSCLC (n=8), melanoma (n=7), other (n=7). Extracranial disease was present in ten (45%) patients. The median number of tumors was 3 (range 1–6). The median overall survival was 31 weeks. The median radiographic follow-up for patients that did not develop DBF was 33 weeks. Six patients developed DBF. The one year actuarial risk of DBF was 37%. Patients with melanoma had a higher risk of DBF than other patients (p<0.001, log-rank). Only 1/15 patients without melanoma vs. 5/7 patients with melanoma developed DBF. 15 serious adverse events (SAEs) occurred in 10 of the patients, but none of the SAEs were judged to be likely related to temozolomide. Among patients that experienced DBF, no significant differences were seen in QOL when pretreatment FACT-Br and time of distant brain failure FACT-Br scores were compared. Conclusions: Adjuvant temolozomide after radiosurgery is associated with a low risk of distant brain failure in non-melanoma patients. Larger clinical trials should examine the relative efficacy and QOL of WBRT and temozolomide in non-melanoma brain metastases patients. No significant financial relationships to disclose.

Radiosurgery alone for solitary and multiple brain metastasis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1541-1541
Author(s):  
J. L. Fox ◽  
L. Kleinberg ◽  
S. Kharkar ◽  
R. E. Clatterbuck ◽  
P. Wang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Median Number ◽  
Rank Test ◽  
Small Cell Lung ◽  
Treatment Groups ◽  
Time Commitment ◽  
Whole Brain Radiation ◽  
Log Rank Test ◽  
Brain Radiation

1541 Background: Whole-brain radiation (WBRT) in the management of brain metastases treated with radiosurgery (RS) is controversial. Methods: Ninety-eight patients were treated for brain metastases with RS at Johns Hopkins between 4/03 and 7/05. Twenty-eight patients received RS alone after failing WBRT, 33 received RS alone for initial metastases and 37 received RS along with WBRT. Forty-five patients were women and 53 were men, with a median age of 56 (range, 18–92). Histology was: non-small cell lung cancer - 35, breast -14, melanoma -10, renal cell carcinoma - 9, and other - 30. Ninety-two (94%) pts had a KPS of ≥ 70 (median 80). The median number of metastases was 2 (range, 1–14). Results: Follow-up data from date of RS was available for 96 patients. Among those who received RS along with planned WBRT, median survival (MS) was 6.6 months with 1-yr overall survival (OS) 38%. Among patients treated initially with RS alone, MS was 9.7 months with 1-yr OS 42%. Among patients treated with RS for recurrent metastases after prior WBRT, MS was 6.8 months with 1-yr OS 24%. There were no significant differences in survival amongst these 3 treatment groups (p=0.73, log-rank test). For patients with 1–3 metastases (n=66), 1-yr OS was 38% versus 32% for those with ≥ 4 (n=32). Median survivals were 8.4 and 6.7 months, respectively (p=NS). Of patients treated with RS for recurrence, 7 of 25 (28%) with available follow-up data developed recurrent or new metastases whereas 11/27 (41%) treated with RS and planned WBRT and 15/27 (56%) who had RS alone as initial treatment had documented recurrent or new metastases. Conclusions: RS alone may be an effective treatment that preserves survival for those with single or multiple brain metastases at initial presentation or recurrence, but the tradeoff between the marginal increase in risk of brain recurrence versus toxicity and time commitment for WBRT needs further evaluation. The ongoing US Intergroup randomized trial, N0572/Z300, will address some of these questions. No significant financial relationships to disclose.

A phase II trial of temozolomide and vinorelbine for patients with recurrent brain metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2050-2050
Author(s):  
F. M. Iwamoto ◽  
A. M. Omuro ◽  
J. J. Raizer ◽  
C. P. Nolan ◽  
A. Hormigo ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Minor Response ◽  
Radiographic Response ◽  
Whole Brain Radiation ◽  
Heavily Pretreated ◽  
Grade 3

2050 Background: Temozolomide has shown modest efficacy in the treatment of recurrent brain metastases. We designed a regimen combining temozolomide with vinorelbine, a lipophilic agent that crosses the blood-brain barrier, trying to improve efficacy. Methods: This is a phase II trial with 28-day cycles using temozolomide (150 mg/m2, days 1–7 and 15–21) and vinorelbine on days 1 and 8. We previously reported a phase I trial that established an MTD of 30 mg/m2 of vinorelbine in this combination, but the dose was decreased to 25 mg/m2 in this phase II trial. The phase II component was planned as a two-stage clinical trial. Since two or more responses were observed after the 20 initial patients, 15 more assessable patients were required. This design had a 91% probability to detect a true response rate of 20% or more. The primary endpoint was objective radiographic response. Secondary endpoints include OS, PFS and toxicity. Patients = 18 years old with KPS = 60, adequate organ function and progressive or recurrent brain metastases were eligible. Results: Thirty-six patients (13 men, 23 women) with a median age of 56 years (range, 38–76) and median KPS of 80 were enrolled. The primary tumor sites were lung (n=19), breast (n=11), colon (n=2), bladder (n=1), endometrium (n=1), head/neck (n=1) and kidney (n=1). Prior therapies included whole-brain radiation therapy (81%), chemotherapy (97%), radiosurgery (42%) and brain metastasis resection (47%). Objective radiographic response was 7% (1 CR and 1 minor response); 4 patients had SD and 23 PD. Three patients withdrew consent and did not undergo follow-up scans, 2 patients did not receive the planned treatment and 2 patients recently began treatment and have not been assessed. The median follow-up was 12.3 weeks and 72% of patients have died. Median PFS and OS were 8.3 weeks and 5 months, respectively. Grade 3/4 toxicities were mainly hematological and 3 patients were removed from the study due to myelosuppression. Conclusions: In this heavily pretreated population of patients with brain metastases, adding vinorelbine to temozolomide does not seem to improve response rates as compared to temozolomide alone. Single-agent temozolomide also has a more favorable toxicity profile. [Table: see text]

scholarly journals RADI-27. ROLE OF STEREOTACTIC RADIOSURGERY IN THE CARE OF PATIENTS WITH >/= 25 CUMULATIVE BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i27-i27
Author(s):  
Carolina Benjamin ◽  
Monica Mureb ◽  
Bernadine Donahue ◽  
Erik Sulman ◽  
Joshua Silverman ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Tumor Volume ◽  
Median Number ◽  
Median Dose ◽  
Total Tumor Volume ◽  
Whole Brain Radiation ◽  
Brain Radiation

Abstract INTRODUCTION: Stereotactic radiosurgery (SRS) is an accepted treatment for multiple brain metastases. However, the upper limit of the number of brain metastases over the course of care suitable for this approach is controversial. METHODS: From a review of our prospective registry, 48 patients treated with SRS for ≥ 25 brain metastases in either single or multiple sessions between 2013 and 2019 were identified. Patient, tumor, and treatments characteristics were evaluated. Clinical outcomes and overall survival (OS) were analyzed. RESULTS: Thirty-one females (64.6%) and 17 males (35.4%) with a median age of 56 years (25–91) were included. Primary diagnoses included lung (n=23, 47.9%), breast (n=13, 27.1%), melanoma (n=8, 16.7%), and other (n=4, 8.33%). Initial median GPA index was 2 (0.5–3). Nine patients (18.8%) had received whole brain radiation therapy (WBRT) prior to first SRS treatment, with a median dose of 35Gy (30–40.5Gy). Ten patients (20.8%) received WBRT after initial SRS, with a median dose of 30Gy (20-30Gy). Thus, only 19 patients (40%) ever received WBRT. Median number of radiosurgeries per patient was 3 (1–12). Median number of cumulative tumors irradiated was 31 (25–110). Median number of tumors irradiated at first SRS was 10 (1–35). Median marginal dose for the largest tumor per session was 16Gy (10-21Gy). Median SRS total tumor volume was 6.8cc (0.8–23.4). Median follow-up since initial SRS was 16 months (1–71). At present, 21 (43.7%) are alive. Median OS from the diagnosis of brain metastases was 31 months (2–97), and OS from the time of first SRS, 22 months (1–70). Median KPS at first SRS and last follow-up was the same (90). Sixty-three percent did not require a corticosteroid course. CONCLUSION: In selected patients with a large number of cumulative brain metastases (≥ 25), SRS is effective and safe. Therefore, WBRT may not be required in this population.

Incidence, timing, and treatment of new brain metastases after Gamma Knife surgery for limited brain disease: the case for reducing the use of whole-brain radiation therapy

2011 ◽  
Vol 115 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Stephen Rush ◽  
Robert E. Elliott ◽  
Amr Morsi ◽  
Nisha Mehta ◽  
Jeri Spriet ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastases ◽  
Gamma Knife ◽  
Gamma Knife Surgery ◽  
Whole Brain Radiation Therapy ◽  
Leptomeningeal Disease ◽  
Whole Brain ◽  
Whole Brain Radiation ◽  
Brain Radiation

Object In this paper, the authors' goal was to analyze the incidence, timing, and treatment of new metastases following initial treatment with 20-Gy Gamma Knife surgery (GKS) alone in patients with limited brain metastases without whole-brain radiation therapy (WBRT). Methods A retrospective analysis of 114 consecutive adults (75 women and 34 men; median age 61 years) with KPS scores of 60 or higher who received GKS for 1–3 brain metastases ≤ 2 cm was performed (median lesion volume 0.35 cm3). Five patients lacking follow-up data were excluded from analysis. After treatment, patients underwent MR imaging at 6 weeks and every 3 months thereafter. New metastases were preferentially treated with additional GKS. Indications for WBRT included development of numerous metastases, leptomeningeal disease, or diffuse surgical-site recurrence. Results The median overall survival from GKS was 13.8 months. Excluding the 3 patients who died before follow-up imaging, 12 patients (11.3%) experienced local failure at a median of 7.4 months. Fifty-three patients (50%) developed new metastases at a median of 5 months. Six (7%) of 86 instances of new lesions were symptomatic. Most patients (67%) with distant failures were successfully treated using salvage GKS alone. Whole-brain radiotherapy was indicated in 20 patients (18.3%). Thirteen patients (11.9%) died of neurological disease. Conclusions For patients with limited brain metastases and functional independence, 20-Gy GKS provides excellent disease control and high-functioning survival with minimal morbidity. New metastases developed in almost 50% of patients, but additional GKS was extremely effective in controlling disease. Using our algorithm, fewer than 20% of patients required WBRT, and only 12% died of progressive intracranial disease.

scholarly journals Isolated Pubic Ramus Fractures Are Serious Adverse Events for Elderly Persons: An Observational Study on 138 Patients with Fragility Fractures of the Pelvis Type I (FFP Type I)

2020 ◽  
Vol 9 (8) ◽  
pp. 2498 ◽  
Author(s):  
Pol Maria Rommens ◽  
Johannes Christof Hopf ◽  
Michiel Herteleer ◽  
Benjamin Devlieger ◽  
Alexander Hofmann ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Normal Population ◽  
Fragility Fractures ◽  
Type I ◽  
Elderly Persons ◽  
Serious Adverse Events ◽  
Pubic Ramus ◽  
One Year

Background: Fractures of the pubic ramus without involvement of the posterior pelvic ring represent a minority of fragility fractures of the pelvis (FFP). The natural history of patients suffering this FFP Type I has not been described so far. Material and methods: All patients, who were admitted with isolated pubic ramus fractures between 2007 and mid-2018, have been reviewed. Epidemiologic data, comorbidities, in-hospital complications, and one-year mortality were recorded. Of all surviving patients, living condition before the fracture and at follow-up was noted. Mobility was scored with the Parker Mobility Score, quality of life with the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L), subjective sensation of pain with the Numeric Rating Scale (NRS). Results: A consecutive series of 138 patients was included in the study. There were 117 women (84.8%) and 21 men (15.2%). Mean age was 80.6 years (SD 8.6 years). 89.1% of patients presented with comorbidities, 81.2% of them had cardiovascular diseases. Five patients (4%) died during hospital-stay. Median in-hospital stay was eight days (2–45 days). There were in-hospital complications in 16.5%, urinary tract infections, and pneumonia being the most frequent. One-year mortality was 16.7%. Reference values for the normal population of the same age are 5.9% for men and 4.0% for women. One-year mortality rate was 22.2% in the patient group of 80 years or above and 8.8% in the patient group below the age of 80. The rate of surviving patients living at home with or without assistance dropped from 80.5% to 65.3%. The median EQ-5D-Index Value was 0.62 (0.04–1; IQR 0.5–0.78). Reference value for the normal population is 0.78. Average PMS was 4 and NRS 3. Within a two-year period, additional fragility fractures occurred in 21.2% and antiresorptive medication was taken by only 45.2% of patients. Conclusion. Pubic ramus fractures without involvement of the posterior pelvis (FFP Type I) are serious adverse events for elderly persons. During follow-up, there is an excess mortality, a loss of independence, a restricted mobility, and a decreased quality of life. Pubic ramus fractures are indicators for the need to optimize the patient’s general condition.

scholarly journals Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial

2020 ◽  
Author(s):  
Wen-Chi Yang ◽  
Ya-Fang Chen ◽  
Chi-Cheng Yang ◽  
Pei-Fang Wu ◽  
Hsing-Min Chan ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Whole Brain Radiotherapy ◽  
Neurocognitive Function ◽  
Mean Difference ◽  
Whole Brain ◽  
Delayed Recall ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance

Abstract Background Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function. Methods This single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned them to receive HA-WBRT or C-WBRT. Primary endpoint is decline of the Hopkins Verbal Learning Test–Revised (HVLT-R) delayed recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results From March 2015 to December 2018, seventy patients were randomized to yield a total cohort of 65 evaluable patients (33 in the HA-WBRT arm and 32 in the C-WBRT arm) with a median follow-up of 12.4 months. No differences in baseline neurocognitive function existed between the 2 arms. The mean change of HVLT-R delayed recall at 4 months was −8.8% in the HA-WBRT arm and +3.8% in the C-WBRT arm (P = 0.31). At 6 months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, P = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, P = 0.019) and memory score (mean difference = 4.38, P = 0.020) compared with patients undergoing C-WBRT. There were no differences in Trail Making Test Part A or Part B or the Controlled Oral Word Association test between the 2 arms at any time point. There were no differences in brain PFS or OS between arms as well. Conclusion Patients receiving HA-WBRT without memantine showed better preservation in memory at 6-month follow-up, but not in verbal fluency or executive function.

Sign in / Sign up

Export Citation Format

Share Document