scholarly journals A Prospective Phase II Trial of Fractionated Stereotactic Intensity Modulated Radiotherapy With or Without Surgery in the Treatment of Patients With 1 to 3 Newly Diagnosed Symptomatic Brain Metastases

Neurosurgery ◽  
2014 ◽  
Vol 74 (6) ◽  
pp. 586-594 ◽  
Author(s):  
Mario Ammirati ◽  
Varun R. Kshettry ◽  
Tariq Lamki ◽  
Lai Wei ◽  
John C. Grecula
Keyword(s):  
Overall Survival ◽  
Confidence Interval ◽  
Brain Metastases ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Intensity Modulated ◽  
Whole Brain Radiation ◽  
Brain Radiation

ABSTRACT BACKGROUND: Several studies have demonstrated that omitting the routine use of adjuvant whole-brain radiation therapy for patients with newly diagnosed brain metastases may be a reasonable first-line strategy. Retrospective evidence suggests that fractionated stereotactic radiotherapy (fSRT) may have a lower level of toxicity with equivalent efficacy in comparison with radiosurgery. OBJECTIVE: To study the phase II efficacy of using a focally directed treatment strategy for symptomatic brain metastases by the use of fSRT with or without surgery and omitting the routine use of adjuvant whole-brain radiation therapy. METHODS: We used a Fleming single-stage design of 40 patients. Patients were eligible if they presented with 1 to 3 newly diagnosed symptomatic brain metastases, Karnofsky performance scale (KPS) greater than 60, and histological confirmation of primary disease. Patients underwent fSRT with the use of a dose of 30 Gy in 5 intensity-modulated fractions as primary or adjuvant treatment after surgical resection. The primary end point was the proportion of patients who experienced neurological death. Secondary end points were overall survival, time to KPS <70, and progression-free survival. RESULTS: Of 40 patients accrued, 39 were eligible for analysis. The proportion of patients dying of neurological causes was 13% (5 patients), which includes 3 patients with an unknown cause of death. Median overall survival, time to KPS <70, and progression-free survival were 16 (95% confidence interval, 9-23), 14 (95% confidence interval, 7-20), and 11 (95% confidence interval, 4-21) months, respectively. CONCLUSION: A focally directed treatment strategy using fSRT with or without surgery appears to be an effective initial strategy. Based on the results of this phase II clinical trial, further study is warranted.

RTOG 0131: Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligodendrogliomas: Relationship between 1p/19q status and progression-free survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1517-1517 ◽  
Author(s):  
M. A. Vogelbaum ◽  
B. Berkey ◽  
D. Peereboom ◽  
C. Giannini ◽  
R. Jenkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Median Time ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Chromosome 8 ◽  
Newly Diagnosed ◽  
Time To Progression ◽  
Durable Response ◽  
Free Survival

1517 Background: In a previous report, we showed in patients with newly diagnosed anaplastic oligodendrogliomas (AOs) and mixed anaplastic oligoastrocytomas (MAOs) that temozolomide (TMZ) can be given concurrently with radiation therapy (RT) with acceptable toxicity. We have now evaluated the efficacy of this regimen and correlated durability of response with tumor 1p/19q genotype. Methods: A phase II study was performed to evaluate the use of pre-RT TMZ followed by concurrent RT and TMZ in patients with newly diagnosed AO or MAO. The primary endpoint was to determine the pre-RT TMZ six-month progression rate, and secondary endpoints included progression-free survival and overall survival. Results: 40 eligible patients were entered into the trial. Thirty-two patients completed 6 months of pre-RT TMZ and concurrent RT and TMZ. Of the remaining eight patients, 4 withdrew due to toxicity and 4 other patients withdrew from study without evidence of toxicity or pre-RT progression. 1p/19q data are available in 37 cases; 23 tumors had loss of heterozygosity (LOH) of both 1p and 19q (double-deleted) while 14 tumors had LOH of either 1p or 19q (n = 3), or no LOH (n = 11). To date, 11 patients have experienced tumor progression; 1p/19q data are available for 10 of these cases (2 are double-deleted (2/23 = 9%), 8 have at least one intact chromosome (8/14 = 57%). Kaplan-Meier analysis demonstrates that progression free survival is significantly better for the double-deleted group (median time to progression not reached) than for the intact group (median time to progression = 15.2 months, p = 0.001). Overall survival is 98% (39/40) with a median follow-up of 17.5 months (2.8 - 31.1 months). Conclusions: LOH of both 1p and 19q is strongly correlated with a durable response of AO and MAO to a combined regimen of chemotherapy and radiation therapy. Tumors that are intact at 1p and/or 19q progress early despite an aggressive therapeutic regimen. These results suggest that future clinical trials should be prospectively stratified by tumor 1p/19q genotype. [Table: see text]

scholarly journals Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized Trial

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 372 ◽  
Author(s):  
Johanna Buchroithner ◽  
Friedrich Erhart ◽  
Josef Pichler ◽  
Georg Widhalm ◽  
Matthias Preusser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dendritic Cells ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Severe Toxicity ◽  
Newly Diagnosed ◽  
Skin Reactions ◽  
Local Skin ◽  
Free Survival ◽  
Newly Diagnosed Glioblastoma

Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3–20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436–671 versus control: 568 days, 95% CI: 349–680; p = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.

Predicting Tumor Control After Resection Bed Radiosurgery of Brain Metastases

Neurosurgery ◽  
2013 ◽  
Vol 73 (6) ◽  
pp. 1001-1006 ◽  
Author(s):  
Neal Luther ◽  
Douglas Kondziolka ◽  
Hideyuki Kano ◽  
Seyed H. Mousavi ◽  
Johnathan A. Engh ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Tumor Progression ◽  
Local Control ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Free Survival ◽  
Whole Brain Radiation ◽  
Brain Radiation

Abstract BACKGROUND: Stereotactic radiosurgery (SRS) to the resection bed of a brain metastasis is an important treatment option. OBJECTIVE: To identify factors associated with tumor progression after SRS of the resection bed of a brain metastasis and to evaluate patterns of failure for patients who eventually had tumor progression. METHODS: We performed a retrospective analysis of 120 patients who underwent tumor bed radiosurgery after an initial gross total resection. The mean imaging follow-up time was 55 weeks. The median margin dose was 16 Gy. Forty-seven patients (39.2%) underwent whole-brain radiation therapy before or shortly after SRS. RESULTS: Local tumor control was achieved in 103 patients (85.8%). Progression-free survival was 96% at 6 months, 87% at 12 months, and 74% at 24 months. Recurrence most commonly occurred deep in the cavity (65%) outside the planned treatment volume (PTV) margin (53%). PTV, cavity diameter, and a margin dose < 16 Gy significantly correlated with local failure. For patients with PTVs ≥ 8.0 cm3, local progression-free survival declined to 93% at 6 months, 83% at 12 months, and 65% at 24 months. Development or progression of distant metastases occurred in 40% of patients. Whole-brain radiation therapy was not associated with improved local control. CONCLUSION: Resection bed SRS for brain metastases provided excellent local control. The cavity PTV is predictive of tumor control. Because failure usually occurs outside the PTV, inclusion of a judicious 2- to 3-mm margin beyond the area of postoperative enhancement may be prudent.

scholarly journals Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Achiraya Teyateeti ◽  
Paul D Brown ◽  
Anita Mahajan ◽  
Nadia N Laack ◽  
Bruce E Pollock
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Median Overall Survival ◽  
Recursive Partitioning ◽  
Leptomeningeal Disease ◽  
Resection Cavity ◽  
Whole Brain Radiation ◽  
Class 1 ◽  
Outcome Comparison ◽  
Brain Radiation

Abstract Background To compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity. Methods Twenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed. Results Patients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively. Conclusions Following BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

A Phase 2, Randomized, Open-Label Study of Irosustat Versus Megestrol Acetate in Advanced Endometrial Cancer

2017 ◽  
Vol 27 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Patricia Pautier ◽  
Ignace Vergote ◽  
Florence Joly ◽  
Bohuslav Melichar ◽  
Elzbieta Kutarska ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Adverse Events ◽  
Confidence Interval ◽  
Progression Free Survival ◽  
Megestrol Acetate ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Recurrent Endometrial Cancer

ObjectiveAdvanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer.MethodsThis was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor–positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety.ResultsSeventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0–31.4) versus 40 weeks (90% confidence interval, 16.3–64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2.ConclusionsAlthough irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.

A prospective data analysis of targeted therapy combined with concurrent radiation therapy for brain metastasis from NSCLC with driver gene mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14006-e14006
Author(s):  
Xiaotong Duan ◽  
Xiaoxia Zhu ◽  
Lijuan Wang
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Gene Mutation ◽  
Progression Free Survival ◽  
Driver Gene ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Concurrent Radiotherapy ◽  
Nsclc Patients

e14006 Background: Previous studies have shown that brain metastases of non-small cell lung cancer (NSCLC) with positive driver genes have poor prognosis. There is still lack of prospective studies on the efficacy and safety of targeted therapy combined with concurrent radiotherapy for brain metastases(BM). Methods: NSCLC patients, with ECOG score 0-2, having MRI confirmed brain or meningeal metastases were eligible. Patients must have driver gene mutation and received corresponding targeted therapy. The intracranial radiotherapy regimen was SRS or whole brain radiotherapy. The primary objective was iPFS (intracranial progression-free survival); Secondary objectives were: iORR (intracranial objective response rate), PFS (progression-free survival), OS (overall survival). MMSE (Mini Mental State Examination) and FACT-Br was carried out before/after weekly radiotherapy and during systematic treatment. Treatment-related toxicities were assessed according RTOG/EORTC criteria. Tumor responses were evaluated using RECIST V1.1 criteria. Survival analysis was performed using the Graphprism version 6.0 by Kaplan-Meier method and log-rank test. Results: 23 NSCLC with BM was included. Among them, 10 patients were newly diagnosed with NSCLC BM. 2 patients’ BM progressed after targeted therapy. 11 NSCLC patients were newly diagnosed with BM after targeted therapy. 91.3% of patients presented an EGFR mutation, including primarily EGFR 19-exon deletion, EGFR 21-L8585R. 11.5% presented with c-MET mutation. Median age was 58.34 yrs(44-71yrs). Patients were mostly treated with Erolotinib and Gefitinib. All patients were adenocarcinoma. At last follow-up, for patients newly diagnosed with NSCLC BM, 8 patients had achieved intracranial progression, and 7 patients had reached OS, of which 1 died before completing WBRT. The median iPFS was 9.3m(95%CI:0.571-4.055) and the median OS was 11.9m (95%CI:0.2752 -2.732). As for patients who progressed after targeted therapy, one patient’s OS was 4.4m, iPFS of the other patient was 3.9m. Among NSCLC patients who were newly diagnosed with BM after targeted therapy, 8 patients had achieved intracranial progression and 5 patients had reached OS. The median iPFS was 6.13m (95%CI:0.247-1.751) and the mOS was 13.8m (95%CI:0.3660-3.634). Common adverse effects include dry skin, fatigue, dizziness, headache, anorexia, and grade I myelosuppression and no serious adverse events (SAEs); MMSE and FACT-Br scores were no significant differences at baseline and follow-up. Conclusions: In stage IV brain metastatic NSCLC with driver gene mutation, targeted therapy combined with concurrent radiotherapy for BM is tolerable, and there is no significant impact on the quality of life and cognitive function after radiotherapy. The evaluation of efficacy requires further follow-up. Support:LC2019ZD009,81972853 and 81572279.

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