Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review

Ghidini, Michele; Petrelli, Fausto; Hahne, Jens C.; Giorgi, Annamaria; Toppo, Laura; Pizzo, Claudio; Ratti, Margherita; Barni, Sandro; Passalacqua, Rodolfo; Tomasello, Gianluca

doi:10.1007/s12032-017-0919-0

Cited by 24 publications

(31 citation statements)

References 67 publications

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“…However, the likelihood of developing brain metastases varies dramatically depending on the underlying disease. For example, brain metastases are common in lung cancer, breast cancer, and melanoma, but <4% of patients with gastrointestinal (GI) primary malignancies develop brain metastases . Notably, despite this low frequency, given the high prevalence of colorectal cancer, 7%–8% of all patients with cancer and brain metastases have colorectal primary malignancies .…”

Section: Introductionmentioning

confidence: 99%

Enrichment of HER2 Amplification in Brain Metastases from Primary Gastrointestinal Malignancies

et al. 2018

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Background In nongastric gastrointestinal (GI) cancers, HER2‐positive (HER2+) disease is not common. In breast cancer, HER2 status is associated with increased risk of brain metastases and response to HER2‐targeted therapy. The purpose of this project was to compare HER2 status in GI cancer brain metastases versus matched prior sites of disease in order to determine if HER2+ disease is more common intracranially. Materials and Methods We identified 28 patients with GI cancer who had craniotomy for brain metastases between 1999 and 2017 with intracranial metastatic tissue available at Massachusetts General Hospital. Twenty‐four patients also had tissue from a prior site of disease. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for HER2 were performed on all samples. A tumor was defined as HER2+ if it had 3+ staining by IHC or amplification by FISH. Results A prior site of disease (including intracranial metastases) was HER2+ for 13% of evaluable patients: 3 of 11 patients with colorectal cancer and no patients with esophageal or pancreatic cancer. The most recent brain metastases were HER2+ for 32% of patients: 2 of 3 esophageal squamous cell carcinomas, 3 of 10 esophageal adenocarcinomas (ACs), 3 of 14 colorectal ACs, and 1 of 1 pancreatic AC. Only 37.5% of patients with HER2+ brain metastasis had concordant HER2+ prior tissue (κ = 0.38, p = .017). Conclusion In this cohort of patients with GI cancer with brain metastases, HER2+ status was more common intracranially compared with prior sites of disease. These findings suggest that testing HER2 in patients with GI cancer with brain metastases may lead to additional therapeutic options, regardless of HER2 status in previously examined tissue. Implications for Practice HER2 amplification is a well‐known driver of oncogenesis in breast cancer, with associated increased risk of brain metastases and response to HER2‐directed therapy. In nongastric gastrointestinal (GI) cancers, HER2 amplification is not common and consequently is infrequently tested. The current study shows that brain metastases in patients with GI primary malignancies have a relatively high likelihood of being HER2 positive despite HER2 amplification or overexpression being less commonly found in matched tissue from prior sites of disease. This suggests that regardless of prior molecular testing, patients with GI cancer with brain metastases who have tissue available are likely to benefit from HER2 assessment to identify potential novel therapeutic options.

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Section: Introductionmentioning

confidence: 99%

Enrichment of HER2 Amplification in Brain Metastases from Primary Gastrointestinal Malignancies

et al. 2018

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“…Another trial suggested that patients who underwent stereotactic radiosurgery plus post‐operative WBRT show better local control and overall survival than those who underwent stereotactic radiosurgery alone, with a median survival of only 16.7 months . However, there is a lack of consensus about the best way to manage brain metastases of gastric and oesophageal primary tumours, with a variety of different interventions used (eg surgery, RT, WBRT or multimodality treatments) …”

Section: Discussionmentioning

confidence: 99%

“…12 However, there is a lack of consensus about the best way to manage brain metastases of gastric and oesophageal primary tumours, with a variety of different interventions used (eg surgery, RT, WBRT or multimodality treatments). 13 The blood-brain barrier is composed of different cell types and provides a stable microenvironment for the CNS, 6 which protects brain metastases from cytotoxic agents, thereby lowering CSF penetration of chemotherapeutic drugs. 14 However, apatinib (397.5 daltons) may have a limited ability to penetrate the blood-brain barrier when brain metastases increase the permeability of the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Combination of apatinib and continuous nutritional support for a gastric cancer patient with brain metastasis prolongs survival

Yang

Pei

Mi³

2018

J Clin Pharm Ther

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“…With the introduction of targeted agents and immune checkpoint inhibitors, for kidney cancer, malignant melanoma, HER-2-positive breast cancer, and subsets of non-small-cell lung cancer, selected patients can now undergo upfront systemic therapy of their brain metastases [3-9]. However, sequential radiotherapy and systemic therapy continue to play a role in the interdisciplinary management of patients with brain metastases [10-14]. Achieving control of both brain and extracranial disease is a prerequisite for prolonged survival.…”

Section: Introductionmentioning

confidence: 99%

Recursive Partitioning Analysis of Systemic Therapy after Radiotherapy in Patients with Brain Metastases

2021

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Purpose: The purpose of this study was to identify factors associated with the initiation or continuation of systemic treatment after brain irradiation. The outcome of interest was a utilization rate of at least 75%, given that active extracranial disease is common in patients with brain metastases. If left untreated, extracranial disease limits survival, regardless of successful local treatment of the brain metastases. In this context, systemic therapy has been shown to improve survival, e.g., after whole-brain radiotherapy. Patients and Methods: The study included 185 patients with active extracranial disease, 60% of whom received systemic therapy. Results: Survival from the start of brain irradiation was longest in patients who received additional immune checkpoint inhibitors, endocrine treatment, or anti-HER-2 drugs. After uni- and multivariate analyses, Eastern Cooperative Oncology Group performance status (PS) was selected as the first prediction criterion in the recursive partitioning analysis (RPA) decision tree analysis. RPA was successful for patients with PS 0–1, but patients with PS 2 had lower treatment utilization rates (maximum 60–70%, with a disease-dependent impact of age and LabBM score [blood test results]). The highest utilization rates were observed in (1) patients with PS 0 and (2) those with breast cancer, small-cell lung cancer, or lung adenocarcinoma with PS 1. Conclusions: These results inform the multidisciplinary discussion and treatment planning for the common scenario of simultaneous intra- and extracranial metastases.

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Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review

Cited by 24 publications

References 67 publications

Enrichment of HER2 Amplification in Brain Metastases from Primary Gastrointestinal Malignancies

Enrichment of HER2 Amplification in Brain Metastases from Primary Gastrointestinal Malignancies

Combination of apatinib and continuous nutritional support for a gastric cancer patient with brain metastasis prolongs survival

Recursive Partitioning Analysis of Systemic Therapy after Radiotherapy in Patients with Brain Metastases

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