Diagnosis and Treatment of Brain Metastases

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 17462

Special Issue Editors

Department of Radiation Oncology and Department of Neurosurgery, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, 460 W. 10th Ave, Columbus, OH 43210, USA
Interests: benign and malignant diseases of the central nervous system; stereotactic radiosurgery; gamma knife radiosurgery; proton therapy; heavy ion therapy
Special Issues, Collections and Topics in MDPI journals
Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA
Interests: central nervous system malignancies; stereotactic radiosurgery; immunotherapy; tumor microenvironment; functional radiosurgery; clinical trials; novel cellular therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The incidence of brain metastasis is increasing as improvements in systemic therapy lead to increased survival. This provides challenging clinical decisions for patients who are trying to balance the risk of progression of disease with treatment-related side effects, and it requires management strategies from diverse multidisciplinary teams. Improvements in systemic therapy with increasing activity in the brain allows for individualized care to better guide the use of local therapies and systemic therapy. Here, we discuss treatment strategies including targeted therapies for patients with actionable mutations, immunotherapy, whole-brain radiation therapy, radiosurgery, surgery/laser interstitial thermal therapy, and modern clinical trials.

We look forward to receiving your contributions.

Dr. Joshua D. Palmer
Dr. Daniel M. Trifiletti
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (9 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

13 pages, 3285 KiB  
Article
Low-Dose Bevacizumab for the Treatment of Focal Radiation Necrosis of the Brain (fRNB): A Single-Center Case Series
by Jens Tijtgat, Evan Calliauw, Iris Dirven, Manon Vounckx, Randa Kamel, Anne Marie Vanbinst, Hendrik Everaert, Laura Seynaeve, Dirk Van Den Berge, Johnny Duerinck and Bart Neyns
Cancers 2023, 15(9), 2560; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15092560 - 29 Apr 2023
Cited by 3 | Viewed by 1655
Abstract
Focal radiation necrosis of the brain (fRNB) is a late adverse event that can occur following the treatment of benign or malignant brain lesions with stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS). Recent studies have shown that the incidence of fRNB is [...] Read more.
Focal radiation necrosis of the brain (fRNB) is a late adverse event that can occur following the treatment of benign or malignant brain lesions with stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS). Recent studies have shown that the incidence of fRNB is higher in cancer patients who received immune checkpoint inhibitors. The use of bevacizumab (BEV), a monoclonal antibody that targets the vascular endothelial growth factor (VEGF), is an effective treatment for fRNB when given at a dose of 5–7.5 mg/kg every two weeks. In this single-center retrospective case series, we investigated the effectiveness of a low-dose regimen of BEV (400 mg loading dose followed by 100 mg every 4 weeks) in patients diagnosed with fRNB. A total of 13 patients were included in the study; twelve of them experienced improvement in their existing clinical symptoms, and all patients had a decrease in the volume of edema on MRI scans. No clinically significant treatment-related adverse effects were observed. Our preliminary findings suggest that this fixed low-dose regimen of BEV can be a well-tolerated and cost-effective alternative treatment option for patients diagnosed with fRNB, and it is deserving of further investigation. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)
Show Figures

Figure 1

11 pages, 3403 KiB  
Article
Sodium Fluorescein-Guided Surgery for Resection of Brain Metastases from Lung Cancer: A Consecutive Case Series Study and Literature Review
by Xing Cheng, Jie Chen, Ronghua Tang, Jian Ruan, Deqiang Mao and Haifeng Yang
Cancers 2023, 15(3), 882; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030882 - 31 Jan 2023
Cited by 2 | Viewed by 1312
Abstract
(1) Introduction and objective: Surgical resection plays an important role in the multidisciplinary treatment of lung cancer patients with brain metastases (BMs). Precisely distinguishing the tumor border intraoperatively to improve and maximize the extent of resection (EOR) without causing permanent neurological defects is [...] Read more.
(1) Introduction and objective: Surgical resection plays an important role in the multidisciplinary treatment of lung cancer patients with brain metastases (BMs). Precisely distinguishing the tumor border intraoperatively to improve and maximize the extent of resection (EOR) without causing permanent neurological defects is crucial but still challenging. Therefore, we introduced our experience of utilizing sodium fluorescein (SF) in microneurosurgery of BMs from lung cancer. This study aims to evaluate whether the use of SF-guided surgery has a positive impact on postoperative outcomes. (2) Materials and methods: A retrospective study was performed to collect data on a consecutive case series of patients with BMs from lung cancer who underwent surgical resection from January 2020 to December 2021 at the Department of Neuro-Oncology, Chongqing University Cancer Hospital. A total of 52 patients were enrolled, of which 23 received SF-guided surgery and 29 did not. EOR was assessed pre- and postoperatively on T1 contrast-enhanced MRI. Clinical and epidemiological data as well as follow-up were gathered and analyzed. (3) Results: Compared with the non-SF-guided group, the SF-guided group revealed a significantly better EOR (87.0% vs. 62.1%) and a lower incidence of local recurrence (8.7% vs. 34.5%). Survival benefits were seen in patients with NSCLC, patients who were undergoing SF-guided surgery, and patients receiving postoperative systemic therapy. (4) Conclusions: SF-guiding under the YELLOW 560 nm filter is a safe and feasible tool for improving the EOR in patients with BMs from lung cancer, leading to better local recurrence control and prolonged survival. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)
Show Figures

Figure 1

11 pages, 1048 KiB  
Article
Zero Setup Margin Mask versus Frame Immobilization during Gamma Knife® Icon™ Stereotactic Radiosurgery for Brain Metastases
by Tugce Kutuk, Rupesh Kotecha, Ranjini Tolakanahalli, D Jay J. Wieczorek, Yongsook C. Lee, Manmeet S. Ahluwalia, Matthew D. Hall, Michael W. McDermott, Haley Appel, Alonso N. Gutierrez, Minesh P. Mehta and Martin C. Tom
Cancers 2022, 14(14), 3392; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143392 - 13 Jul 2022
Cited by 5 | Viewed by 1720
Abstract
We compared the clinical outcomes of BM treated with mask immobilization with zero-SM (i.e., zero-PTV) to standard zero-SM frame immobilization SRS. Consecutive patients with BM, 0.5–2.0 cm in maximal diameter, treated with single-fraction SRS (22–24 Gy) during March 2019–February 2021 were included. Univariable [...] Read more.
We compared the clinical outcomes of BM treated with mask immobilization with zero-SM (i.e., zero-PTV) to standard zero-SM frame immobilization SRS. Consecutive patients with BM, 0.5–2.0 cm in maximal diameter, treated with single-fraction SRS (22–24 Gy) during March 2019–February 2021 were included. Univariable and multivariable analysis were performed using the Kaplan–Meier method and Cox proportional hazards regression. A total of 150 patients with 453 BM met inclusion criteria. A total of 129 (28.5%) lesions were treated with a zero-SM mask immobilization and 324 (71.5%) with zero-SM frame immobilization. Frame immobilization treatments were associated with a higher proportion of gastrointestinal and fewer breast-cancer metastases (p = 0.024), and a higher number of treated lesions per SRS course (median 7 vs. 3; p < 0.001). With a median follow up of 15 months, there was no difference in FFLF between the mask and frame immobilization groups on univariable (p = 0.29) or multivariable analysis (p = 0.518). Actuarial FFLF at 1 year was 90.5% for mask and 92% for frame immobilization (p = 0.272). Radiation necrosis rates at 1 year were 12.5% for mask and 4.1% for frame immobilization (p = 0.502). For BM 0.5–2.0 cm in maximal diameter treated with single-fraction SRS using 22–24 Gy, mask immobilization with zero SM produces comparable clinical outcomes to frame immobilization. The initial findings support omitting a SM when using mask immobilization with this treatment approach on a Gamma Knife® Icon™. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)
Show Figures

Figure 1

9 pages, 543 KiB  
Article
Benchmarking Safety Indicators of Surgical Treatment of Brain Metastases Combined with Intraoperative Radiotherapy: Results of Prospective Observational Study with Comparative Matched-Pair Analysis
by Motaz Hamed, Anna-Laura Potthoff, Julian P. Layer, David Koch, Valeri Borger, Muriel Heimann, Davide Scafa, Gustavo R. Sarria, Jasmin A. Holz, Frederic Carsten Schmeel, Alexander Radbruch, Erdem Güresir, Niklas Schäfer, Patrick Schuss, Stephan Garbe, Frank A. Giordano, Ulrich Herrlinger, Hartmut Vatter, Leonard Christopher Schmeel and Matthias Schneider
Cancers 2022, 14(6), 1515; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14061515 - 16 Mar 2022
Cited by 11 | Viewed by 3410
Abstract
Intraoperative radiotherapy (IORT) of the operative cavity for surgically treated brain metastasis (BM) has gained increasing prominence with respect to improved local tumor control. However, IORT immediately performed at the time of surgery might be associated with increased levels of perioperative adverse events [...] Read more.
Intraoperative radiotherapy (IORT) of the operative cavity for surgically treated brain metastasis (BM) has gained increasing prominence with respect to improved local tumor control. However, IORT immediately performed at the time of surgery might be associated with increased levels of perioperative adverse events (PAEs). In the present study, we performed safety metric profiling in patients who had undergone surgery for BM with and without IORT in order to comparatively analyze feasibility of IORT as an adjuvant radiation approach. Between November 2020 and October 2021, 35 patients were surgically treated for BM with IORT at our neuro-oncological center. Perioperative complication profiles were collected in a prospective observational cohort study by means of patient safety indicators (PSIs), hospital-acquired conditions (HACs), and specific cranial-surgery-related complications (CSCs) as high-standard quality metric tools and compared to those of an institutional cohort of 388 patients with BM resection without IORT in a balanced comparative matched-pair analysis. Overall, 4 out of 35 patients (11%) with IORT in the course BM resection suffered from PAEs, accounting for 3 PSIs (9%) and 1 HAC (3%). Balanced matched-pair analysis did not reveal significant differences in the perioperative complication profiles between the cohorts of patients with and without IORT (p = 0.44). Thirty-day mortality rates were 6% for patients with IORT versus 8% for patients without IORT (p = 0.73). The present study demonstrates that IORT constitutes a safe and clinically feasible adjuvant treatment modality in patients undergoing surgical resection of BM. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)
Show Figures

Figure 1

Review

Jump to: Research, Other

13 pages, 310 KiB  
Review
Current Treatment of Melanoma Brain Metastases
by Agnieszka Nowacka, Anna Fajkiel-Madajczyk, Jakub Ohla, Kamila Woźniak-Dąbrowska, Sara Liss, Karol Gryczka, Wojciech Smuczyński, Ewa Ziółkowska, Dominika Bożiłow, Maciej Śniegocki and Michał Wiciński
Cancers 2023, 15(16), 4088; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15164088 - 14 Aug 2023
Cited by 4 | Viewed by 1251
Abstract
Melanoma is a type of skin cancer in which there is a strong correlation between its occurrence and exposure to ultraviolet radiation. Although it is not the most common skin cancer, it has the highest mortality rate of all skin cancers. The prognosis [...] Read more.
Melanoma is a type of skin cancer in which there is a strong correlation between its occurrence and exposure to ultraviolet radiation. Although it is not the most common skin cancer, it has the highest mortality rate of all skin cancers. The prognosis of patients is significantly worsened by melanoma metastasis to the brain, which often occurs in patients with advanced disease. The formation and development of melanoma metastases to the brain involve a very complex process, and their mechanisms are not fully understood. One of the ways for metastatic melanoma cells to survive and develop cancer in the brain environment is the presence of oncogenic BRAF mutation, which occurs in up to 50% of metastatic melanoma cases. Before discovering new methods of treating metastases, the overall survival of patients with this disease was 6 months. Currently, research is being conducted on new drugs using immunotherapy (immune checkpoint inhibitors: anti-PD-1, anti-CTLA-4) and targeted therapy (BRAF and MEK inhibitors) to improve the prognosis of patients. In this article, we summarize the current state of knowledge about the results of treating brain metastases with new systemic therapies. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)
15 pages, 2912 KiB  
Review
Management of Brain Metastases from Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer
by Tresa M. McGranahan, Alipi V. Bonm, Jennifer M. Specht, Vyshak Venur and Simon S. Lo
Cancers 2022, 14(20), 5136; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14205136 - 20 Oct 2022
Viewed by 1543
Abstract
In the past 5 years, the treatment options available to patients with HER2+ breast cancer brain metastasis (BCBM) have expanded. The longer survival of patients with HER2+ BCBM renders understanding the toxicities of local therapies even more important to consider. After reviewing the [...] Read more.
In the past 5 years, the treatment options available to patients with HER2+ breast cancer brain metastasis (BCBM) have expanded. The longer survival of patients with HER2+ BCBM renders understanding the toxicities of local therapies even more important to consider. After reviewing the available literature for HER2 targeted systemic therapies as well as local therapies, we present a simplified algorithm for when to prioritize systemic therapies over local therapies in patients with HER2+ BCBM. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)
Show Figures

Figure 1

9 pages, 558 KiB  
Review
Surgical Management of Recurrent Brain Metastasis: A Systematic Review of Laser Interstitial Thermal Therapy
by Mark A. Damante, Jr., Joshua L. Wang and J. Bradley Elder
Cancers 2022, 14(18), 4367; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14184367 - 08 Sep 2022
Cited by 1 | Viewed by 1410
Abstract
The incidence of recurrent metastatic brain tumors is increasing due to advances in local therapy, including surgical and radiosurgical management, as well as improved systemic disease control. The management of recurrent brain metastases was previously limited to open resection and/or irradiation. In recent [...] Read more.
The incidence of recurrent metastatic brain tumors is increasing due to advances in local therapy, including surgical and radiosurgical management, as well as improved systemic disease control. The management of recurrent brain metastases was previously limited to open resection and/or irradiation. In recent years, laser interstitial thermal therapy (LITT) has become a promising treatment modality. As systemic and intracranial disease burden increases in a patient, patients may no longer be candidates for surgical resection. LITT offers a relatively minimally invasive option for patients that cannot tolerate or do not want open surgery, as well as an option for accessing deep-seated tumors that may be difficult to access via craniotomy. This manuscript aims to critically review the available data regarding the use of LITT for recurrent intracranial brain metastasis. Ten of seventy-two studies met the criteria for review. Generally, the available literature suggests that LITT is a safe and feasible option for the treatment of recurrent brain metastases involving supratentorial and cortical brain, as well as posterior fossa and deep-seated locations. Among all studies, only one directly compared craniotomy to LITT in the setting of recurrent brain metastasis. Prospective studies are needed to better elucidate the role of LITT in the management of recurrent brain metastases. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)
Show Figures

Figure 1

17 pages, 360 KiB  
Review
Quality of Life and Cognitive Function Evaluations and Interventions for Patients with Brain Metastases in the Radiation Oncology Clinic
by Jennifer K. Matsui, Haley K. Perlow, Cyril Baiyee, Alex R. Ritter, Mark V. Mishra, Joseph A. Bovi, Vinai Gondi, Paul D. Brown, Ashlee R. Loughan, Heather E. Leeper, Erica Dawson and Joshua D. Palmer
Cancers 2022, 14(17), 4301; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14174301 - 01 Sep 2022
Cited by 4 | Viewed by 2108
Abstract
Brain metastases (BMs) account for a disproportionately high percentage of cancer morbidity and mortality. Historically, studies have focused on improving survival outcomes, and recent radiation oncology clinical trials have incorporated HRQOL and cognitive assessments. We are now equipped with a battery of assessments [...] Read more.
Brain metastases (BMs) account for a disproportionately high percentage of cancer morbidity and mortality. Historically, studies have focused on improving survival outcomes, and recent radiation oncology clinical trials have incorporated HRQOL and cognitive assessments. We are now equipped with a battery of assessments in the radiation oncology clinic, but there is a lack of consensus regarding how to incorporate them in modern clinical practice. Herein, we present validated assessments for BM patients, current recommendations for future clinical studies, and treatment advances that have improved HRQOL and cognitive outcomes for BM patients. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)

Other

Jump to: Research, Review

19 pages, 1968 KiB  
Systematic Review
The Evolving Landscape of Leptomeningeal Cancer from Solid Tumors: A Systematic Review of Clinical Trials
by Lina Marenco-Hillembrand, Michael A. Bamimore, Julio Rosado-Philippi, Blake Perdikis, David N. Abarbanel, Alfredo Quinones-Hinojosa, Kaisorn L. Chaichana and Wendy J. Sherman
Cancers 2023, 15(3), 685; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030685 - 22 Jan 2023
Viewed by 2135
Abstract
Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5–15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2–6 months. We aimed to conduct a systematic review [...] Read more.
Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5–15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2–6 months. We aimed to conduct a systematic review of the literature to identify past and future therapies for LMC from solid tumors. Forty-three clinical trials (CTs) published between 1982–2022 were identified. Of these, 35 (81.4%) were non-randomized CTs and 8 (18.6%) were randomized CTs. The majority consisted of phase I (16.3%) and phase II CTs (65.1%). Trials enrolled patients with LMC from various primary histology (n = 23, 57.5%), with one CT evaluating LCM from melanoma (2.4%). A total of 21 trials evaluated a single modality treatment. Among CTs, 23.7% closed due to low accrual. Intraventricular (ITV)/intrathecal (IT) drug delivery was the most common route of administration (n = 22, 51.2%) vs. systemic drug delivery (n = 13, 30.3%). Two clinical trials evaluated the use of craniospinal irradiation for LMC with favorable results. LMC continues to carry a dismal prognosis, and over the years, increments in survival have remained stagnant. A paradigm shift towards targeted systemic therapy with continued standardization of efficacy endpoints will help to shed light on promising treatments. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Brain Metastases)
Show Figures

Figure 1

Back to TopTop