Toxicity Of Whole Brain Radiotherapy Research Articles

Thirty-Year Experience of Radiotherapy for Primary Intraocular Lymphoma with and without Chemotherapy.

Primary intraocular lymphoma (PIOL) is a rare presentation of primary central nervous system lymphoma (PCNSL). We previously reported that ocular radiation therapy (RT) is an excellent option that can spare appropriate patients' upfront toxicity of whole brain radiotherapy (WBRT) and aggressive chemotherapy. A decade later, we expanded this series with almost double median follow up time. We identified all patients seen at our institution from 1990-2022 treated for PCNSL or who received RT to the orbits. Detailed chart review was completed for cases with isolated ocular involvement at presentation (PIOL) who received RT to unilateral or bilateral orbits. Patients with disease on MRI brain or CSF cytology were excluded. Analysis included Kaplan-Meier method, log-rank-test, and Wilcoxon rank sum test. Overall survival (OS) was measured from diagnosis. Freedom-from-recurrence (FFR) measured time from RT start to first recurrence identified on imaging (parenchymal), slit-lamp exam (ocular), or biopsy. A total of 75 patients were treated with RT to the orbits as part of management of PCNSL. 29 had PIOL with median follow up of 52 months from diagnosis. Of this subset, 22 (76%) received RT at our institution, median age at diagnosis was 65 (31-84) and 18 (62%) had bilateral disease. The majority were diagnosed by vitrectomy or vitreoretinal biopsy with B-cell lymphoma or unspecified lymphoma and 3 were clinically diagnosed. 17 patients received RT alone, 10 received RT after induction chemotherapy and 2 with induction and consolidation chemotherapy. Younger patients received chemotherapy (median age 60 vs 70, p = 0.03). RT dose ranged from 30 to 45 Gy, and 20 (69%) received 36 Gy, primarily with 1.8 Gy fractions. 22 (76%) received RT to bilateral orbits. 21 (72%) developed recurrence (Table 1), of which 6 (28.5%) recurred in a RT-treated eye and 11 (52.4%) isolated in the brain. 2 got salvage orbital RT and 4 got WBRT. Median OS was 5.4 years (95% CI 3.9, 7.6) and FFR was 8.4 months (95% CI 5.0, 25). There was no difference in OS (p = 0.4) or FFR (p = 0.3) between combined modality therapy versus RT alone. In this updated experience, we demonstrate that RT alone remains an effective option for isolated PIOL, especially for those at risk of poor toleration of chemotherapy. Systemic therapy or WBRT can be utilized at recurrence, which primarily occurs in the brain. Future comparisons are needed to compare orbital RT to intravitreal therapies, and to investigate how these methods can complement each other to further improve management.

Inter Fraction Target Dynamics and Variability Between T1 and T2-Weighted MRI During Surgical Cavity Hypofractionated Stereotactic Radiotherapy: Prospective Serial Imaging Study

Hypofractionated stereotactic radiotherapy (HSRT) to surgically resected brain metastases is a standard option to reduce local recurrence and spare the toxicity of whole brain radiotherapy. This study examined changes in the clinical target volume (CTV) and associated variations in brain parenchyma dosimetry on a 1.5T MRI linear accelerator. In addition, the suitability of using T2/FLAIR (T2f) as a surrogate to define CTV was explored by assessing contouring variability between different standard MRI sequences during treatment.Fifteen patients were prospectively imaged with gadolinium-enhanced T1 (T1c) and T2f axial sequences at the time of planning (FxSim) and at fraction 3 (Fx3) of HSRT to the cavity. Clinical target volumes (CTV) were contoured at both time points on T1c and T2f sequences. All patients were treated with either 27.5Gy or 30Gy in 5 fractions. The total volume of brain minus CTV receiving 30Gy (V30Gy) was obtained at both time points on T1c sequence. Inter-fraction surgical cavity dynamics and CTV delineation variability were quantified using absolute volume, Dice similarity coefficient (DC) and Hausdorff distance (HD) metrics.The median time from surgery to HSRT was 22 days. The median CTVs on T1c and T2f sequences at FxSim were 12cm3 (range, 1.2-30.1) and 10.2cm3 (range, 2.9-27.9), respectively. At Fx3, the median CTV decreased slightly in both sequences to 9.7cm3 (range, 3.7-25.9) and 8.7cm3 (range, 2.9-24.9), translating to a median % reduction in CTV compared to FxSim of 11.7% on T1c and 8.9% on T2f, respectively (P < 0.05). The mean V30Gy for all patients at FxSim and Fx3 were 6.14cm3 (range 0.11-15.7) and 7.17cm3 (range 0.15-20.1), respectively (P < 0.05). We observed a reduction in CTV volume in 12/15 (80%) patients on T1c at Fx3 relative to FxSim. Two patients that had a reduction in CTV volumes at Fx3 developed radionecrosis (RN) on follow up MRI and recorded a mean V30Gy of 10.8cm3 at FxSim and 13.6cm3 at Fx3. The mean DC was 0.831 (range 0.688-0.905) and the mean HD was 6.32mm (range 2.4-12.3) when comparing between CTV volumes contoured on T1c and T2f, indicating variability of CTV delineation between the two sequences.Clinically meaningful changes in target dynamics were observed during the course of cavity irradiation, supporting the use of MR image guided radiation therapy and treatment adaptation. We also observed variability in CTV delineation between T1c and T2f sequences, highlighting the importance of further work in this field.

Whole brain radiotherapy concurrent with capecitabine chemotherapy for patients with brain metastases from post-operative breast cancer

Objective To evaluate the efficacy and toxicity of whole brain radiotherapy concurrent with capecitabine for treatment of brain mestastases from breast cancer with post-operative.Methods Fifty patients with brain mestastases from breast cancer with post-operative were randomized into two groups:25 patiens were treatend with whole brain radiotherapy concurrent with capecitabine (treatment group) and the other 25 patients were treated with whole brain radiotherapy alone (control group).Radiation dose was 40 Gy in 20 fractions over 4 weeks.Capecitabine was administered concurrently with radiotherapy in escalatiny dose from the 1st day of RT to the end day (850 mg/m2,twice/day).Results The survival rates at 1-and 2-year were 60.0 ％ (15/25) and 28.0 ％ (7/25) in treatment group,44.0 ％ (11/25) and 16.0 ％ (4/25) in control group (x2 =1.28,1.05,P ＞ 0.05).Toxicities were tolerable.Conclusion Whole brain radiotherapy concurrent with capecitabine was effective and safe in treatment for patients with breat cancer and well-tolerated toxicity. Key words: Breast neoplasms; Neoplasm metastasis; Capecitabine; Radiotherapy

Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma

BackgroundTo retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT) in patients with multiple brain metastases (BM) from malignant melanoma (MM).Patients and methodsResults of 87 patients (median age 58 years; 35 female, 52 male) treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56) or 40 Gy in 20 fractions (n = 31). All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients.ResultsMean follow-up was 8 months (range, 0–57 months), the 6- and 12-months overall-(OS) survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11) patients showed a complete (partial) remission, while 11 (17) patients had stable disease (intra-cerebral tumor progression). In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months). Furthermore, DS-GPA score (p < 0.001) as well as RPA class (p < 0.001) influenced significantly on OS and patients had a significantly longer OS after surgical resection (p = 0.001, median 3.0 vs. 5.8 months, multivariate p = 0.007). Having extra-cerebral metastases didn't significantly impact on OS (p = 0.21).ConclusionTreatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.

Addition of upfront whole-brain radiotherapy to surgery or stereotactic radiosurgery versus surgery or stereotactic radiosurgery alone for treatment of brain metastases: A systematic review and meta-analysis.

2016 Background: The benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to determine the efficacy and safety of additional upfront WBRT. Methods: We searched MEDLINE, EMBASE, CENTRAL from date of inception and annual meeting proceedings of ASCO and ASTRO from 1999 to September 2011 for RCTs comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), quality of life (Qol) and neurological toxicity. Hazard ratios (HR), confidence intervals (CI), p values (p) were estimated with random effects models using Revman 5.1. Results: We found five RCTs including 663 patients with one to four brain metastases. Adding upfront WBRT decreased the one-year incidence of any intracranial disease progression from 73-76% to 22 - 47% but did not improve OS (HR 1.11, 95%CI 0.83 - 1.48, p = 0.47) and PFS (HR 0.76, 95%CI 0.53 - 1.10, p = 0.14). Subgroup analyses showed that the effects on overall survival are similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The effects of upfront WBRT on NF, Qol and neurological toxicity were variable. Conclusions: Adding upfront WBRT to surgery or SRS significantly decreased any intracranial disease progression at one year but did not improve overall and progression free survival and produced variable effects on neurocognitive function, quality of life and neurological toxicity when compared with surgery or SRS alone. Future research should focus on developing more effective approaches to characterize and ameliorate the potential neurological toxicity of WBRT.

Chemotherapy as primary treatment for brain metastases from breast cancer: analysis of 115 one-year survivors

Given the potential toxicity of whole brain radiotherapy, we introduced systemic therapy as possible primary treatment for brain metastases (BM) from breast cancer. This study aims to evaluate the feasibility of this therapeutic approach. Review of 115 breast cancer patients treated for BM with at least 1 year of follow-up. Patients with single BM without extracranial disease were usually treated with surgery, patients with multiple BM and controlled extracranial disease usually with RT, and those with progressive extracranial disease usually with systemic therapy as primary treatment for BM. Primary treatment for BM was surgery in 30 patients, RT in 26 patients, RT combined with systemic therapy in 33 patients, and systemic therapy as single treatment in 27 patients (chemotherapy n = 20; hormonal therapy n = 7). Response rate to surgery was 100 %, to RT 85 %, to RT+systemic therapy 87 %, to chemotherapy 70 %, and to hormonal therapy 14 %. Duration of neurological response and of extracranial response to chemotherapy as single treatment was similar (8 and 7 months, respectively). Patients with single BM and patients without extracranial disease had a better survival but the difference was not significant. Chemotherapy as single treatment for BM from breast cancer is feasible and should not be restricted to salvage treatment.

Efficacy and Toxicity of Whole Brain Radiotherapy plus Simultaneous Image Guided Intensity Modulation Radiotherapy Boost for Brain Metastases of NSCLC

Efficacy and Toxicity of Whole Brain Radiotherapy plus Simultaneous Image Guided Intensity Modulation Radiotherapy Boost for Brain Metastases of NSCLC

Phase I Study of Concurrent Whole Brain Radiotherapy and Erlotinib for Multiple Brain Metastases From Non–Small-Cell Lung Cancer

Erlotinib has shown activity in patients with brain metastases from non-small-cell lung cancer. The present dose-escalation Phase I trial evaluated the toxicity of whole brain radiotherapy (WBRT) with concurrent and maintenance erlotinib in this patient group. Erlotinib (Cohort 1, 100 mg/d; Cohort 2, 150 mg/d) was started 1 week before, and continued during, WBRT (30 Gy in 10 fractions). Maintenance erlotinib (150 mg/d) was continued until unacceptable toxicity or disease progression. A total of 11 patients completed WBRT, 4 in Cohort 1 and 7 in Cohort 2. The median duration of erlotinib treatment was 83 days. No treatment-related neurotoxicity was observed. No treatment-related Grade 3 or greater toxicity occurred in Cohort 1. In Cohort 2, 1 patient developed a Grade 3 acneiform rash and 1 patient had Grade 3 fatigue. Two patients in Cohort 2 developed erlotinib-related interstitial lung disease, contributing to death during maintenance therapy. The median overall survival and interval to progression was 133 and 141 days, respectively. Six patients developed extracranial progression; only 1 patient had intracranial progression. In 7 patients with follow-up neuroimaging at 3 months, 5 had a partial response and 2 had stable disease. WBRT with concurrent erlotinib is well tolerated in patients with brain metastases from non-small-cell lung cancer. The suggestion of a high intracranial disease control rate warrants additional study.

Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

Delayed toxicity of whole brain radiotherapy (WBRT) in germ cell tumor (GCT) patients with central nervous system (CNS) metastases

15511 Background: CNS metastases are uncommon in GCT. Incidence is 2–3% and is usually associated with extensive pulmonary metastases and/or high serum human chorionic gonadotropin levels. CNS metastases have been managed with WBRT and concomitant cisplatin-based combination chemotherapy. Our prior publication did not observe serious CNS toxicity (Int J Rad Oncol Biol Phys 22:17–22, 1991). Methods: We observed 5 patients with delayed CNS toxicity. Initial diagnosis was 1981 through 2003. Median age 23 years (range 21–34). All 5 patients had advanced disease by the International Germ Cell Consensus Collaborative Group. Three of five patients had CNS metastases at the time of diagnosis, and two patients relapsed with CNS metastases. These 5 patients received WBRT 4,000–5,000 cGy in 18- 28 fractions concurrently with cisplatin-based chemotherapy. Results: All five patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy (PMLE), including seizures, hemiparesis, expressive and receptive aphasia, cranial neuropathies including facial droop, tremors, headaches, blindness, dementia, decreased level of consciousness, ataxia, and parasthesias. Median time from WBRT to CNS symptoms was 72 months (range 9–228 months). Brain imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. One patient was diagnosed with glioblastoma multiforme in the area of radiation-induced gliosis. 3 of 5 patients had progressive symptoms, and the other 2 had stable symptoms. Treatment with surgery and steroids had modest benefit. The PMLE resulted in significant debility in all five patients, resulting in death (2 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations. Conclusions: WBRT is not innocuous in young patients with GCT and can cause late CNS toxicity. We are now cautious about the use of WBRT and reserve it for multiple CNS metastases that are symptomatic or resistant to chemotherapy. No significant financial relationships to disclose.