Asymptomatic cystic changes in the brain of children after cranial irradiation: frequency, latency, and relationship to age

7644 Background: With increasing use of MRI and PET to stage NSCLC, the demographics, performance status and distribution of metastases at diagnosis in this patient (pt) population are changing; it is important to reassess the prognostic roles played by baseline clinical variables in the modern therapeutic era. Methods: We retrospectively evaluated the charts of 189 consecutive, unselected pts with stage IV NSCLC seen and followed at the Fox Chase Cancer Center between Oct 2000 and Aug 2003. Data on a variety of pt variables including demographics, histology, metastases, key laboratory tests and treatment were compiled. We intended to identify those that played statistically significant prognostic roles. Results: Median age at diagnosis was 62 years; 77% of pts had PS 0–1 at first presentation. 58% had single organ metastasis; 35% had metastases to the brain (half of these had brain only and a third had solitary brain metastasis). 51% of all pts received palliative radiation to the brain at some point after dx. Overall median survival was 10.8 months. The 1-yr, 2-yr, 3-yr and 4-yr overall survival rates were 44.2%, 21.9%, 11.6% and 7.8% respectively. On multivariate analysis, statistically significant negative prognostic factors included PS ≥ 2 (HR: 1.9, 95% CI: 1.1–3.3), serum albumin ≤ 3 (HR: 1.7, 95% CI: 1.1–2.8) and metastases to > 1 organ (HR: 1.6, 95% CI: 1.03–2.3). Bone and liver metastases, though associated with worse survival in univariate analysis, were not found to be independent predictors of survival. Gender had no bearing on outcome. Conclusions: Survival rates in this advanced NSCLC cohort equal or exceed contemporaneous ECOG figures. PS, serum albumin and number of organs with metastases are independent prognostic factors in NSCLC. The increasing detection of brain metastases at 1st presentation of metastatic NSCLC suggests that the role of prophylactic cranial irradiation in the management of early NSCLC should be explored. No significant financial relationships to disclose. [Table: see text]

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First-line durvalumab plus platinum-etoposide in extensive-stage (ES)-SCLC (CASPIAN): Impact of brain metastases on treatment patterns and outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9068 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9068-9068

Author(s):

Yuanbin Chen ◽

Luis G. Paz-Ares ◽

Mikhail Dvorkin ◽

Dmytro Trukhin ◽

Niels Reinmuth ◽

...

Keyword(s):

Brain Metastases ◽

Cranial Irradiation ◽

Prophylactic Cranial Irradiation ◽

Treatment Patterns ◽

First Line ◽

Open Label ◽

Treatment Naïve ◽

Extensive Stage ◽

Post Hoc ◽

The Brain

9068 Background: In the Phase 3, randomized, open-label CASPIAN study, first-line durvalumab (D) added to etoposide plus either cisplatin or carboplatin (EP) significantly improved OS vs EP alone (HR 0.73 [95% CI 0.59–0.91]; p = 0.0047) in pts with ES-SCLC at the planned interim analysis. Here we describe treatment patterns and outcomes for pts according to brain metastases. Methods: Treatment-naïve pts (WHO PS 0/1) with ES-SCLC received 4 cycles of D 1500 mg + EP q3w followed by maintenance D 1500 mg q4w until disease progression (PD) or up to 6 cycles of EP q3w and optional prophylactic cranial irradiation (PCI; investigator’s discretion). Pts with either asymptomatic or treated and stable brain metastases were eligible. Brain imaging was suggested for pts with suspected brain metastases, but was not mandated at screening or during treatment. The primary endpoint was OS. Analysis of OS and PFS in pt subgroups with and without brain metastases was prespecified. Other analyses in these subgroups were post hoc. Data cutoff: Mar 11, 2019. Results: At baseline, 28 (10.4%) of 268 pts in the D + EP arm and 27 (10.0%) of 269 pts in the EP arm had known brain metastases; of these, only 3 pts (~11% of those with baseline brain metastases) in each arm received radiotherapy (RT) to the brain prior to study entry. D + EP consistently improved OS vs EP in pts with or without known brain metastases at baseline (HR 0.69 [95% CI 0.35–1.31] and 0.74 [0.59–0.93], respectively); PFS was also consistently improved with D + EP regardless of the presence or not of baseline brain metastases (HR 0.73 [0.42–1.29] and 0.78 [0.64–0.95]). Among pts without known brain metastases at baseline, similar proportions developed new brain metastases at first PD in the D + EP (20/240; 8.3%) and EP arms (23/242; 9.5%), despite 19 (7.9%) pts in the EP arm having received PCI. Overall, 48 of 268 (17.9%) and 49 of 269 (18.2%) pts in the D + EP and EP arms received RT to the brain subsequent to study treatment; rates remained similar across the D + EP and EP arms regardless of baseline brain metastases (11 of 28 [39.3%] and 11 of 27 [40.7%] pts with known baseline brain metastases, compared to 37 of 240 [15.4%] and 38 of 242 [15.7%] pts without known baseline brain metastases). Conclusions: In CASPIAN, OS and PFS outcomes were improved with D + EP vs EP regardless of baseline brain metastases, consistent with the ITT analyses. Rates of new brain metastases at first PD were similar between arms, although PCI was permitted only in the control arm. Rates of subsequent RT to the brain were also similar in both arms. Clinical trial information: NCT03043872.

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Pulsed reduced dose-rate radiotherapy for previously irradiated tumors in the brain and spine

Surgical Neurology International ◽

10.25259/sni_589_2020 ◽

2021 ◽

Vol 12 ◽

pp. 280

Author(s):

Arpan V. Prabhu ◽

Madison Lee ◽

Edvaldo Galhardo ◽

Madison Newkirk ◽

Analiz Rodriguez ◽

...

Keyword(s):

Dose Rate ◽

Cranial Irradiation ◽

Recurrent Glioblastoma ◽

Precentral Gyrus ◽

Management Options ◽

Thoracic Spinal Cord ◽

Reduced Dose ◽

Thoracic Spinal ◽

The Brain

Background: Patients with unresectable locoregional cancer recurrences have limited management options. Reirradiation increases the risk of toxicity, particularly when perilesional dose-volume constraints are exceeded. We present and discuss two cases of previously irradiated tumors in the central nervous system (CNS) that was reirradiated using the pulsed reduced dose-rate radiotherapy (PRDR) technique. Case Description: A 58-year-old female with a history of metastatic small cell lung cancer to the brain status post multiple rounds of radiation and chemotherapy presented with increasing weakness in her right arm and leg. Magnetic resonance imaging (MRI) revealed a growly peripherally enhancing 1.2 cm mass in the left precentral gyrus that had previously received prophylactic cranial irradiation and stereotactic radiosurgery. The patient was re-irradiated with 35 Gy in 100 fractions over 3 weeks, using PRDR with improved motor function at 3-month follow-up. A 41-year-old male with recurrent glioblastoma of the thoracic spinal cord presented with worsening neurological symptoms, including inability to ambulate due to bilateral leg weakness, causing wheelchair use. MRI thoracic spine revealed a recurrent thoracic lesion 2.2 × 1 × 0.8 cm. In addition to chronic chemotherapy, the patient was retreated palliatively in the same area at 50 Gy in 250 fractions, over 6 weeks, using PRDR. The treated lesion was stable on follow-up imaging, and the patient was able to walk with the assistance of a walker. Conclusion: In our two cases, PRDR proved effective in the treatment of recurrent malignant CNS tumors that were previously irradiated. Prospective studies are needed to delineate the efficacy and toxicity of PRDR.

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Outcomes of prophylactic cranial irradiation in patients with small cell lung cancer in the modern era of baseline magnetic resonance imaging of the brain

Acta Oncologica ◽

10.1080/0284186x.2021.1974553 ◽

2021 ◽

pp. 1-8

Author(s):

Mads Kjaergaard Held ◽

Olfred Hansen ◽

Tine Schytte ◽

Karin Holmskov Hansen ◽

Rana Bahij ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Lung Cancer ◽

Magnetic Resonance ◽

Cranial Irradiation ◽

Prophylactic Cranial Irradiation ◽

Small Cell ◽

Resonance Imaging ◽

Small Cell Lung ◽

Modern Era ◽

The Brain

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Ataxia-Telangiectasia: Atypical Presentation and Toxicity of Cancer Treatment

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100007794 ◽

2009 ◽

Vol 36 (4) ◽

pp. 462-467 ◽

Cited By ~ 18

Author(s):

Rochelle A. Yanofsky ◽

Sashi S. Seshia ◽

Angelika J. Dawson ◽

Kent Stobart ◽

Cheryl R. Greenberg ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Ataxia Telangiectasia ◽

Cancer Susceptibility ◽

Cranial Irradiation ◽

Atypical Presentation ◽

Lymphoid Malignancies ◽

Neuroectodermal Tumors ◽

Progressive Cerebellar Ataxia ◽

Severe Infections ◽

The Brain

Background:The onset of progressive cerebellar ataxia in early childhood is considered a key feature of ataxiatelangiectasia (A-T), accompanied by ocular apraxia, telangiectasias, immunodeficiency, cancer susceptibility and hypersensitivity to ionizing radiation.Methods:We describe the clinical features and course of three Mennonite children who were diagnosed with A-T following the completion of therapy for lymphoid malignancies.Results:Prior to cancer therapy, all had non-progressive atypical neurological abnormalities, with onset by age 30 months, including dysarthria, dyskinesia, hypotonia and/or dystonia, without telangiectasias. Cerebellar ataxia was noted in only one of the children and was mild until his death at age eight years. None had severe infections. All three children were “cured” of their lymphoid malignancies, but experienced severe adverse effects from the treatments administered. The two children who received cranial irradiation developed supratentorial primitive neuroectodermal tumors of the brain, an association not previously described, with fatal outcomes.Conclusions:The range of neurological presentations of A-T is broad. Ataxia and telangiectasias may be minimal or absent and the course seemingly non-progressive. The diagnosis of A-T should be considered in all children with neuromotor dysfunction or peripheral neuropathy, particularly those who develop lymphoid malignancies. The consequences of missing the diagnosis may be dire. Radiation therapy and radiomimetic drugs should be avoided in individuals with A-T.

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Primary anaplastic astrocytoma of the brain after prophylactic cranial irradiation in a case of acute lymphoblastic leukemia: Case report and review of the literature

Indian Journal of Medical and Paediatric Oncology ◽

10.4103/0971-5851.133729 ◽

2014 ◽

Vol 35 (1) ◽

pp. 86 ◽

Cited By ~ 2

Author(s):

Imtiaz Ahmed ◽

Sapna Krishnamurthy ◽

Aanchal Kakkar ◽

PramodKumar Julka ◽

GouraKishor Rath

Keyword(s):

Case Report ◽

Acute Lymphoblastic Leukemia ◽

Anaplastic Astrocytoma ◽

Lymphoblastic Leukemia ◽

Cranial Irradiation ◽

Prophylactic Cranial Irradiation ◽

Review Of The Literature ◽

The Brain

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BSCI-18. ABLATION OF Csf2 MITIGATES RADIATION-INDUCED NEUROCOGNITIVE DECLINE INDEPENDENT OF HIPPOCAMPAL NEUROGENESIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.016 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i4-i4

Author(s):

Sölen Gokhan ◽

Kyle Aronson ◽

Yagiz Altun ◽

Violeta Chitu ◽

N Patrik Brodin ◽

...

Keyword(s):

Neural Development ◽

Cognitive Functions ◽

Cognitive Abilities ◽

Cranial Irradiation ◽

Hippocampal Neurogenesis ◽

High Dose ◽

Suitable Alternative ◽

Selective Targeting ◽

Radiation Induced ◽

The Brain

Abstract PURPOSE: The results of the RTOG 0933 and NRG CC001 clinical trials have shown that physical sparing of the hippocampus during cranial irradiation (CI) is associated with preservation of memory functions at 4- and 6-months following therapy. Whereas the putative roles of protection of neural stem cells (NSCs) residing within the subgranular zone (SGZ) of the dentate gyrus are presently poorly defined, suppression of inflammation may be involved because ablation of microglia (MG) through blockade of the CSF-1R or selective targeting of CCR2+ macrophages using an appropriate CCR2 inhibitor leads to the retention of hippocampal-dependent cognitive abilities following CI. Inhibition of Colony stimulating factor 2 (CSF-2), a proinflammatory cytokine causing the proliferation and activation of microglia, may be a suitable alternative strategy to alleviate inflammation. METHODS: Our studies have evaluated the effects of ablation of Csf2 and also the inducible ablation of MG on the properties of neuroinflammation, neurogenesis and CI-associated cognitive impairments employing the requisite mouse models. RESULTS: We demonstrate that preservation of cognitive functions following CI does not require ablation of MG. In addition, the reduction in neuroinflammation following Csf2ablation was sufficient to prevent CI-induced cognitive decline. Moreover, Csf2 ablation did not prevent the deficit in neurogenesis, thereby suggesting that NSC-mediated SGZ neurogenesis is not required for the prevention of radiation-induced cognitive dysfunction. CONCLUSION: We have previously shown that MG play seminal roles in neural development and adult homeostasis and plasticity. Our present study demonstrates that selective modulation of MG-associated neuroinflammatory signaling without MG ablation is a novel therapeutic strategy to preserve cognitive functions following CI. These experimental observations have seminal implications for patients undergoing radiation therapy for tumors of the brain or head and neck in which the hippocampus inevitably exposed to a high dose of radiation leading to potentially debilitating and possibly avoidable cognitive deficits.

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