Improving Brain Metastases Outcomes Through Therapeutic Synergy Between Stereotactic Radiosurgery and Targeted Cancer Therapies

Rubino, Sebastian; Oliver, Daniel; Tran, Nam; Vogelbaum, Michael A.; Yu, Hsiang‐Hsuan Michael; Ahmed, Kamran A.; Etame, Arnold B.

doi:10.3389/fonc.2022.854402

Cited by 16 publications

(9 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SRS and SRT have increasingly used as an alternative to WBRT in patients with BM [ 20 ]. Based on randomized studies comparing SRS vs WBRT plus SRS, SRS is the current recommended treatment in patients with a limited number of BM (1–4).…”

Section: Discussionmentioning

confidence: 99%

“…At the same manner, immune checkpoint inhibitors (ICI) anti PD-1/PDL-1 (nivolumab, pembrolizumab, atezolizumab, durvalumab) and anti-CTLA-4 inhibitors (Ipilimumab, tremelimumab) are increasingly used for treating patients with advanced disease [ 12 – 14 ], whilst combining targeted- and immune-based therapies is being evaluated in a variety of solid tumors [ 15 ]. Notably, according to the ability of these drug to penetrate the blood–brain barriers, targeted- and immune-based therapies, alone or in combination, have shown a therapeutic efficiency in treating BM [ 5 – 8 ], whilst increasing evidence suggest their use in combination with radiotherapy (RT) [ 16 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov

et al. 2023

View full text Add to dashboard Cite

Background The management of brain metastases (BM), the major cause of cancer morbidity and mortality, is becoming an emerging area of interest. Surgery, whole brain radiation therapy (WBRT), or stereotactic radiosurgery (SRS), have historically been the main focal treatments for BM. However, the introduction of innovative targeted- and immune-based therapies is progressively changing the paradigm of BM treatment, resulting in an increase in clinical trials investigating new therapeutic strategies. Methods Using ClinicalTrials.gov, the largest clinical trial registry with over 400,000 registered trials, we performed an analysis of phase II and phase III ongoing trials evaluating different systemic therapies, radiotherapy (RT), and surgery given alone or in combination in patients with BM. Results One hundred sixty-eight trials, 133 phase II and 35 phase III; the largest part having primarily the curative treatment of patients with BM from lung cancer, breast cancer and melanoma, were selected. One hundred sixty-three trials used systemic therapies. One hundred thirteen used tyrosine kinase inhibitors, more frequently Osimertinib, Icotinib and Pyrotinib, 50 used monoclonal antibodies, more frequently Trastuzumab, Pembrolizumab, Nivolumab, 20 used conventional chemotherapies whilst no oncological active drugs were used in 6 trials. Ninety-six trials include RT; 54 as exclusive treatment and 42 in combination with systemic therapies. Conclusion Systemic targeted- and/or immune-based therapies, combined or not with RT, are increasingly used in the routine of BM treatment. SRS is progressively replacing WBRT. All these trials intend to address multiple questions on the management of patients with BMs, including the recommended upfront treatment for different cancer histologies and the optimal timing between systemic therapies and radiation regarding brain control and neurocognitive outcome and quality of life.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Historically, the utilization of systemic therapy in patients with BMs has been limited by the presence of the blood–brain barrier (BBB), which restricts the entry of hydrophilic and/or large drugs into the brain.) [ 5 , 12 , 19 , 20 ]. Another consideration that might explain the disappointing results of chemotherapy in BM is the fact that metastatic cells in the brain often develop late in the course of the disease; after several rounds of prior chemotherapy for the systemic disease, allowing for the development of resistance through the accumulation of various mutations [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Cetuximab plus XELOX show efficacy against brain metastasis from colorectal cancer: a case report

et al. 2023

View full text Add to dashboard Cite

Brain metastasis (BM) from colorectal cancer (CRC) is rare and associated with poor prognosis. The mainstay of treatment for BM from CRC is radiotherapy, systemic treatment options for CRC can include novel targeted agents, conventional chemotherapy or a combination of both. Nevertheless, the efficacy of these systemic treatment options against BM from CRC is not yet fully established. Cetuximab, a monoclonal antibody, has been shown to be effective in patients with KRAS wild-type metastatic CRC. The combination of cetuximab with oxaliplatin-based chemotherapy is commonly utilized as a systemic treatment for metastatic CRC. Hereby, we report a case of BM from CRC with significant response after capecitabine and oxaliplatin (XELOX) combined with cetuximab.

show abstract

“…SRS and SRT have increasingly used as an alternative to WBRT in patients with BM [20]. Based on randomized studies comparing SRS vs WBRT plus SRS, SRS is the current recommended treatment in patients with a limited number of BM (1-4), and its use has been conditionally recommended up to 10 BM in patients with good performance status [4,28].…”

Section: Discussionmentioning

confidence: 99%

“…At the same manner, immune checkpoint inhibitors (ICI) anti PD-1/PDL-1 (nivolumab, pembrolizumab, atezolizumab, durvalumab) and anti-CTLA-4 inhibitors (Ipilimumab, tremelimumab) are increasingly used for treating patients with advanced disease [12][13][14], whilst combining targeted-and immune-based therapies is being evaluated in a variety of solid tumors [15]. Notably, accordingly to the ability of these drug to penetrate the blood-brain barriers, targeted-and immune-based therapies, alone or in combination, have shown a therapeutic e ciency in treating BM [5][6][7][8], whilst increasing evidence suggest their use in combination with radiotherapy (RT) [16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov

Tini

Marampon

Giraffa³

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: The management of brain metastases (BM), the major cause of cancer morbidity and mortality, is becoming an emerging area of interest. Surgery, whole brain radiation therapy (WBRT), or stereotactic radiosurgery (SRS), have historically been the main focal treatments for BM. However, the introduction of innovative targeted- and immune-based therapies is progressively changing the paradigm of BM treatment, resulting in an increase in clinical trials investigating new therapeutic strategies. Methods: Using ClinicalTrials.gov, the largest clinical trial registry with over 400,000 registered trials, we performed an analysis of phase II and phase III ongoing trials evaluating different systemic therapies, radiotherapy (RT), and surgery given alone or in combination in patients with BM. Results: One hundred sixty-eight trials, 133 phase II and 35 phase III; the largest part having primarily the curative treatment of patients with BM from lung cancer, breast cancer and melanoma, were selected. One hundred sixty-three trials used systemic therapies. One hundred thirteen used tyrosine kinase inhibitors, more frequently Osimertinib, Icotinib and Pyrotinib, 50 used monoclonal antibodies, more frequently Trastuzumab, Pembrolizumab, Nivolumab, 20 used conventional chemotherapies whilst no oncological active drugs were used in 6 trials. Ninety-six trials include RT; 54 as exclusive treatment and 42 in combination with systemic therapies. Conclusions: Systemic targeted- and/or immune-based therapies, combined or not with RT, are increasingly used in the routine of BM treatment. SRS is progressively replacing WBRT. All these trials intend to address multiple questions on the management of patients with BMs, including the recommended upfront treatment for different cancer histologies and the optimal timing between systemic therapies and radiation regarding brain control and neurocognitive outcome and quality of life.

show abstract

Improving Brain Metastases Outcomes Through Therapeutic Synergy Between Stereotactic Radiosurgery and Targeted Cancer Therapies

Cited by 16 publications

References 93 publications

Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov

Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov

Cetuximab plus XELOX show efficacy against brain metastasis from colorectal cancer: a case report

Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov

Contact Info

Product

Resources

About