Efficacy Of Whole Brain Radiotherapy Research Articles

MO56-2 Efficacy of whole brain radiotherapy for patients with leptomeningeal metastasis of non-small cell lung cancer: NEJ049

MO56-2 Efficacy of whole brain radiotherapy for patients with leptomeningeal metastasis of non-small cell lung cancer: NEJ049

Induction bevacizumab, etoposide and cisplatin followed by whole brain radiotherapy (WBRT) versus WBRT alone in breast cancer with untreated brain metastases: Results of a randomized phase II A-PLUS trial.

1082 Background: Our previous study ( Clin Cancer Res. 2015;21(8):1851) demonstrated that bevacizumab preconditioning followed by etoposide and cisplatin (BEEP) is a highly effective treatment for breast cancer (BC) patients (pts) with brain metastases (BM) progressing from WBRT. We conducted a randomized phase II study A-PLUS (NCT02185352) to test whether using BEEP as an induction therapy could enhance the efficacy of WBRT and provide systemic control. Methods: BC pts with measurable BM not suitable for surgery/radiosurgery and had not received WBRT were randomized (2:1) to experimental arm: induction BEEP for 3 cycles (~2 months [ms]) followed by WBRT or control arm: upfront WBRT. The BEEP regimen consists of bevacizumab 15 mg/kg on day 1, and etoposide 70 mg/m2/day on days 2-4, cisplatin 70 mg/m2 on day 2, followed by prophylaxis GCSF, every 21 days. After WBRT in both arms, pts received treatment of physician’s choice except BEEP until BM progression. Stratification was based on the Graded Prognostic Assessment score. Primary endpoint was brain-specific progression free survival (BS-PFS) based on RECIST 1.1, with a total of 108 pts, power of 0.8 at the 2-sided α level of 0.2. Results: Of 112 enrolled pts, 74 were in experimental arm and 38 in control arm. Baseline patient characteristics were generally balanced between arms. With median follow up of 28.7 ms, median BS-PFS was 8.1 vs. 6.5 ms ( p= 0.146; HR 0.71 [95% CI 0.44-1.13]), which met the primary endpoint (pre-defined α level of 0.2). Results of preplanned analysis included: 2-month brain-specific objective response rate of BEEP alone vs. WBRT was 41.9% vs. 52.6% ( p= 0.613); 8-month BS-PFS rate was 48.7% vs. 26.3% ( p= 0.027); median PFS was 6.4 vs. 4.7 ms ( p= 0.071; HR 0.67 [95% CI 0.43-1.04]), and extra-BM PFS was 7.9 vs. 5.0 ms ( p= 0.141; HR 0.71 [95% CI 0.46-1.12]). Median overall survival was 15.6 vs. 13.6 ms ( p= 0.855; HR 0.96 [95% CI 0.59-1.55]), with 31.6% of pts in control arm received BEEP regimen treatment after BM progression. The most common all-grade adverse events (AEs) in experimental arm were neutropenia (30.2%), nausea (27.9%), anemia (27.4%), and leukopenia (24.2%). Most AEs were mild to moderate in severity. Two pts discontinued BEEP treatment due to grade 4 nephrotoxicity and grade 3 infection, respectively. Conclusions: BEEP as induction treatment followed by WBRT for BC pts with BM may improve control of both BM and systemic disease. Further validation by a phase III study is necessary. Clinical trial information: NCT02185352 .

Whole brain radiotherapy with concurrent temozolomide in multifocal and/or multicentric newly diagnosed glioblastoma

The standard medical care of glioblastoma (GBM) patients with good performance status is based on focal brain radiotherapy (40–60 Gy) with concurrent temozolomide (TMZ) followed by adjuvant TMZ. Newly diagnosed multifocal and/or multicentric GBM (M/M GBM) cases are usually treated with TMZ alone: whole brain chemoradiotherapy (CRT) is avoided for safety reasons. To our knowledge, no study has investigated the safety and efficacy of whole-brain radiotherapy (WBRT) with concurrent TMZ in M/M GBM patients. This retrospective study sought to assess the role of WBRT associated with concurrent TMZ followed by TMZ alone in this population. Eleven patients with pathologically proven M/M GBM (≥3 lobes) were treated with WBRT between April 2009 and September 2017. The median age was 50 years [34–74]. The median dose of radiotherapy was 45 Gy at 1.8 Gy per fraction over 37 days [29–41], with concurrent daily TMZ at the dose of 75 mg/m2. This treatment was followed by adjuvant monthly TMZ (150 mg/m2-D1-D5). All pathology slides and radiology images were reviewed. The median overall and progression-free survival times for all patients were 10 months [4–25] and 5 months [3–21], respectively. There was no grade 3–4 toxicity due to radiotherapy. One patient stopped the TMZ during the radiochemotherapy period and 9 patients received adjuvant TMZ with a median number of 5 cycles [2–8]. Our study supports the safety and the efficacy of WBRT with TMZ in newly diagnosed M/M GBM. Larger prospective studies are needed to support our results.

Effectiveness of temozolomide combined with whole brain radiotherapy for non-small cell lung cancer brain metastases.

BackgroundWe performed a retrospective analysis to compare the efficacy of whole brain radiotherapy (WBRT) combined with temozolomide (TMZ) versus WBRT alone as first‐line treatment for brain metastases (BM).MethodsSeventy‐eight non‐small cell lung cancer patients with BM were observed, including 45 patients who received WBRT plus TMZ (TMZ + WBRT) and 33 patients who received WBRT alone (WBRT). The primary outcome was overall survival (OS). Secondary outcomes included progression‐free survival (PFS), objective response rate (ORR), and adverse events.ResultsThe TMZ + WBRT arm achieved significant improvement in ORR (P = 0.0108) compared to the WBRT arm. PFS in the TMZ + WBRT arm was significantly longer than in the RT arm (6.0 vs. 3.5 months; P = 0.038). OS was not significantly different between the two arms. Although increased adverse reactions were experienced in the TMZ + WBRT arm, patients were tolerant of the side effects. Statistically significant differences in neurocognitive function and quality of life were observed between the arms at six months.ConclusionConcomitant TMZ + WBRT compared to WBRT alone significantly increases ORR and median PFS in patients with BM, but no remarkable difference in median OS was found. Adding TMZ to the treatment strategy could prevent neurocognitive function and quality of life from deteriorating. Although the addition of TMZ increases the incidence of adverse effects, no significant difference was observed. Thus, TMZ is safe and effective.

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.

The treatment of patients with 1-3 brain metastases: is there a place for whole brain radiotherapy alone, yet? A retrospective analysis.

To evaluate the efficacy of whole brain radiotherapy (WBRT) with or without other treatments in patients (pts) with 1-3 brain metastases (BM). Toxicities and survival of 134 pts treated between 2009 and 2013 with WBRT alone (58 pts), WBRT plus surgery (SUR-WBRT: 42 pts) or WBRT followed by stereotactic or integrated boost radiotherapy (SRT-WBRT: 34 pts) were analyzed. Differences in toxicity (acute and late) incidence and in overall (OS), disease-free (DFS) and disease-specific survival (DSS) were evaluated (χ(2)-test, uni- and multivariate analysis). Pts given intensified treatments (SUR- and SBRT-WBRT) had better 3-month local response compared to WBRT alone group (p<0.045). Better 1-year local control was evident only in SRT-WBRT pts (p<0.035). Univariate OS analysis confirmed, as favorable prognostic factors, RPA class I (p<0.001), GPA class III and IV (p<0.001), single metastasis (p=0.045), stable primary disease (p=0.03), intensified treatment (p=0.000), systemic therapy after radiotherapy (p=0.04) and response of metastatic lesions (p=0.002). At multivariate analysis, OS was better in RPA class I pts (p=0.002), who had more aggressive radiotherapy treatments (p=0.001), chemotherapy after radiotherapy (p<0.001) and response to RT (p=0.003). Response to radiotherapy (p=0.002) and BM number (p<0.001) resulted independently prognostic for DFS. About 60% of patients had mild acute toxicity (G1), especially headache (51%) and fatigue (34%); only 2 patients (2%) had severe (G3) headache and 5 patients (4%) severe fatigue (G3) reversible with oral steroids. No differences were evident between the different treatment groups. Among 80 pts followed up with MRI, 12 (15%) had leukoencephalopathy (equally distributed across subgroups) and 5 (6%) radionecroses, 4/5 asymptomatic, 5/5 in pts given intensified treatments. This analysis confirms the known prognostic factors for BM, emphasizing the importance of intensified treatments in a population with favorable features.

Radiotherapy concomitant with first-generation epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of brain metastases from non small cell lung cancer: a meta-analysis

To evaluate the efficacy of whole brain radiotherapy (WBRT) or/and stereotactic radiotherapy (SRT) concomitant with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (TKI), like erlotinib and gefitinib, in the treatment of brain metastases from non-small cell lung cancer (NSCLC). Comprehensive searches were performed in different databases, including EMBASE, MEDLINE and Cochrane Library, etc. All randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) comparing radiotherapy (RT) plus TKI with RT alone in the treatment of brain metastases from NSCLC were included for meta-analysis with Cochrane Collaboration's RevMan5. 2 software. The primary end-points were objective remission (OR), disease control (DC) and toxicity while the secondary end-point was overall survival (OS). Three RCTs and one non-randomized controlled trial were selected and included for final analysis. The RT + TKI group had significant improvements in OR rate (RR = 1. 80, P <0. 01) and DC rate (RR = 1. 31, P <0. 01). Meanwhile, rash (RR = 14. 36, P = 0. 003) and diarrhea (RR = 3. 49, P = 0. 005) increased in the RT + TKI group. Yet there was no significant difference in nausea or vomiting (P = 0. 20). For NSCLC with brain metastases, RT plus TKI could improve OR, DC and OS, but there was a higher incidence of rash and diarrhea. There fore future high-quality and prospective RCTs are warranted to confirm the clinical efficacy of RT plus TKI in the treatment of NSCLC with brain metastases.

CNS Complications of Systemic Malignancy amongst patients attending a Radiotherapy facility in Lagos

Introduction: The Central nervous system (CNS) is a frequent a site of relapse of systemic cancer. There are few data available in literature about the frequency and nature of symptomatic histopathological variants of secondary brain/spinal tumours drawn against the gender/age distribution in our environment. Objective: To study the frequency and manifestation of CNS involvement in patients with systemic cancer for a high index of suspicion so that practitioner will have highest index of suspicion to make early diagnosis and treatment in our environment.Material and methods: A total of 119 patients with histological confirmed cases of cancer with secondaries to the CNS, were analysed for this study. Results: CNS metastasis were more common in female (67%) than male (33%) p=0.047. Spinal cord metastasis is the most common type of neurological manifestation (66.9%) with p=0.011. Breast (60.5%) and prostate (21%) were the most common site of primary tumour. Neurological manifestations were mostly associated with advanced Stage tumours (54.9%) (p=0.000). Approximately half of the cases, 56 (54.9%) were presented at late stage (4). Neurological manifestation occurred &lt;6 months (43.1%) after initial diagnosis of the primary tumour. Spinal/radicular pain was the most prevalent among the patients (43%). CT scan/MRI Imaging in (52.6%) and mode of treatment was radiotherapy (99%) of patients. Conclusion: Even though therapy is largely palliative, research should focus on enhancing the efficacy of whole brain radiotherapy and invest in the biosynthesis of synergistic new systemic agents that could also cross the BBB.DOI: http://dx.doi.org/10.3126/ajms.v6i4.11805 Asian Journal of Medical Sciences Vol.6(4) 2015 55-60

Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma

The aim of this paper is to explore the efficacy of whole brain radiotherapy (WBRT) versus WBRT concurrent with erlotinib in patients with multiple brain metastases of lung adenocarcinoma. WBRT was administered at 30Gy/10f in both arms. In the combination arm, 150 mg erlotinib was given each day, starting the first day of radiotherapy and continuing for 1 month following the end of radiotherapy. Thereafter, pemetrexed or docetaxel monotherapy or the best supportive therapy was given to both arms. The intracranial objective response rate and the local progression-free survival (LPFS) were primary endpoints. Toxicity, progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Thirty-one patients in the WBRT group and 23 patients in the combination group were enrolled from November 2009 to December 2011. In the WBRT and the combination arms, respectively, the objective response rate was 54.84% and 95.65% (P = 0.001), the median local progression-free survival was 6.8 months and 10.6 months (P = 0.003), the median PFS was 5.2 months and 6.8 months (P = 0.009), and median OS was 8.9 months and 10.7 months (P = 0.020). In the combination group, there were no differences of LPFS, PFS, and OS between the epidermal growth factor receptor (EGFR) mutation patients and EGFR wild-type patients. No Grade 4 or higher side effects were observed in either group. A multivariate analysis indicated that erlotinib was the most important prognostic factor for a prolonged survival. Data showed that erlotinib in combination with WBRT had a tolerable toxicity profile and prolonged the LPFS, PFS, and OS of lung adenocarcinoma patients with multiple brain metastases compared with WBRT monotherapy.

Whole brain radiotherapy with radiosensitizer for brain metastases

PurposeTo study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment.MethodsA meta-analysis of randomized controlled trials (RCT) was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently.ResultsA total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84–1.25, p = 0.77). Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 – 1.03) and brain tumor progression (OR = 1.11, 95% CI 0.9 – 1.3) when the two arms were compared.ConclusionOur data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide), have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast) to have positive action in lung and breast carcinoma brain metastases in association with WBRT.

Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: A phase II randomized trial

To evaluate the safety profile and efficacy of whole brain radiotherapy (WBRT) concomitantly with temozolomide (TMZ) in patients with brain metastases (BM). Patients with BM were randomly assigned to 30 Gy of WBRT with or without concomitant TMZ (75 mg/m(2)/d) plus two cycles of TMZ (200 mg/m(2)/d for 5 days). The primary outcome was analysis of neurologic toxicity. The primary efficacy measures were 90-day progression-free survival of BM and the radiologic response at Days 30 and 90. We enrolled 82 patients. No neurologic acute toxicity was observed. Grade 3 or worse hematologic toxicity was seen in 3 patients and Grade 3 or worse vomiting in 1 patient of the WBRT plus TMZ arm. The objective response rate at 30 and 90 days and overall survival were similar in both arms. The percentage of patients with progression-free survival of BM at 90 days was 54% for WBRT vs. 72% for WBRT and TMZ (p = 0.03). Death from BM was greater in the WBRT arm (69% vs. 41%, p = 0.03). The concomitant use of RT with TMZ was well tolerated and resulted in significantly better progression-free survival of BM at 90 days. Although caution should be used, these results suggest TMZ could improve local control of BM.

Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study

Background and purpose: To evaluate the efficacy of WBRT as a single treatment modality in patients with brain metastases of small cell lung cancer. Patients and methods: The patients had brain metastases of small cell lung cancer without any sign of tumour outside the brain and were treated with 10×3.0 Gy WBRT. Response and neurological functions were evaluated after 6, 18 and 36 weeks. Results: Twenty of 22 eligible patients were evaluable for response. In six patients a complete response was seen and in five patients a partial response was seen giving a response rate of 50% (95% CI 28–72%). Response duration was 5.4 months (range 63–260 days) and median survival was 4.7 months (range 14–743 days). In the majority of patients the first site of progression after WBRT was in the central nervous system. Twelve of the patients had stabilization or improvement of the neurological function. Conclusion: WBRT for brain metastases of small cell lung cancer gives a 50% response rate with stabilization or improvement of neurological function. Response duration and survival are short.