Outcomes After Whole Brain Reirradiation in Patients With Brain Metastases

Son, Christina H.; Jimenez, Rachel; Niemierko, Andrzej; Loeffler, Jay S.; Oh, Kevin; Shih, Helen A.

doi:10.1016/j.ijrobp.2011.03.020

Cited by 52 publications

(35 citation statements)

References 13 publications

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“…Even if patients initially respond to WBRT, about half will experience recurrence in the brain within 1 year [33] either at the site of previous lesions, or elsewhere.…”

Section: Treatment Of Brain Metastasesmentioning

confidence: 99%

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications

2013

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Breast cancer that has metastasized to the brain presents difficult clinical challenges. This diagnosis comes with high mortality rates, largely due to complexities in early detection and ineffective therapies associated with both dormancy and impermeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) is the current gold standard for diagnosis and assessment of brain tumors. It has been used clinically to investigate metastatic development as well as monitor response to therapy. Here, we describe preclinical imaging strategies that we have used to study the development of brain metastases due to breast cancer. Using this approach, we have identified three subsets of metastatic disease: permeable metastases, nonpermeable metastases, and solitary, dormant cancer cells, which likely have very different biology and responses to therapy. The ability to simultaneously monitor the spatial and temporal distribution of dormant cancer cells, metastatic growth, and associated tumor permeability can provide great insight into factors that contribute to malignant proliferation. Our preclinical findings suggest that standard clinical detection strategies may underestimate the true metastatic burden of breast cancer that has metastasized to the brain. A better understanding of true metastatic burden in brains will be important to assist in the development of more effective chemotherapeutics-particularly those targeted to cross the BBB-as well as detection of small nonpermeable metastases.

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“…Even if patients initially respond to WBRT, about half will experience recurrence in the brain within 1 year [33] either at the site of previous lesions, or elsewhere.…”

Section: Treatment Of Brain Metastasesmentioning

confidence: 99%

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications

2013

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“…While a median OS from the time of repeat RT of 2.7 months is low, it is comparable to most other reirradiation series (Table 4) [6][7][8][9][10][11][12][13]. Notwithstanding the substantial limitations of small retrospective subgroup analysis, we performed an exploratory subgroup analysis and eliminated patients with known poor prognostic histologies (melanomas and small cell lung cancers); the 11 remaining patients were found to have a crude median OS of 6.7 months (Table 3).…”

Section: Discussionmentioning

confidence: 53%

“…The application of this novel technique for the treatment of the whole brain is exciting and may carry promise for further evaluation. Unlike upfront management of brain metastases patients, the literature is relatively limited for guiding treatment of patients with intracranial relapse after WBRT [6][7][8][9][10][11][12][13], despite its occurrence in 47-86% of patients [5]. Furthermore, recommendations are often conflicting, and the existing series span decades over which patient survival and RT delivery techniques have changed significantly [6][7][8][9][10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

“…Potential interventions after WBRT include surgical resection, chemotherapy, SRS, or repeat WBRT. The radiation dose given at the time of repeat WBRT generally is reduced secondary to toxicity concerns and ranges from 20 to 30 Gy [6][7][8][9][10][11][12][13]. This only provides limited biologic effect on gross disease, yet still carries a substantial risk for neurocognitive delay to the patient.…”

Section: Introductionmentioning

confidence: 99%

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Repeat Whole Brain Radiation Therapy with a Simultaneous Infield Boost: A Novel Technique for Reirradiation

Hall

Prabhu

Crocker

et al. 2014

Journal of Radiotherapy

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The treatment of patients who experience intracranial progression after whole brain radiation therapy (WBRT) is a clinical challenge. Novel radiation therapy delivery technologies are being applied with the objective of improving tumor and symptom control in these patients. The purpose of this study is to describe the clinical outcomes of the application of a novel technology to deliver repeat WBRT with volume modulated arc therapy (VMAT) and a simultaneous infield boost (WB-SIB) to gross disease. A total of 16 patients were initially treated with WBRT between 2000 and 2008 and then experienced intracranial progression, were treated using repeat WB-SIB, and were analyzed. The median dose for the first course of WBRT was 35 Gy (range: 30-50.4 Gy). Median time between the initial course of WBRT and repeat WB-SIB was 11.3 months. The median dose at reirradiation was 20 Gy to the whole brain with a median boost dose of 30 Gy to gross disease. A total of 2 patients demonstrated radiographic disease progression after treatment. The median overall survival (OS) time from initial diagnosis of brain metastases was 18.9 months (range: 7.1-66.6 (95% CI: 0.8-36.9)). The median OS time after initiation of reirradiation for all patients was 2.7 months (range: 0.46-14.46 (95% CI: 1.3-8.7)). Only 3 patients experienced CTCAE grade 3 fatigue. No other patients experienced any ≥ CTCAE grade 3 toxicity. This analysis reports the result of a novel RT delivery technique for the treatment of patients with recurrent brain metastases. Side effects were manageable and comparable to other conventional repeat WBRT series. Repeat WB-SIB using the VMAT RT delivery technology is feasible and appears to have acceptable short-term acute toxicity. These results may provide a foundation for further exploration of the WB-SIB technique for repeat WBRT in future prospective clinical trials.

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“…The first was that it was possible for brain metastases to regrow either at previously treated sites or in new locations in the brain (Patchell, 1998). While there are reports of salvage repeat WBRT (Son, 2011;Wong, 1996), the cognitive consequences of radiationinduced leukoencephalopathy were not insignificant. Second, cerebral leukoencephalopathy can also be seen after a single course of WBRT in patients surviving longer than 12 months.…”

Section: Introductionmentioning

confidence: 99%