Prostate Cancer

Long-lasting Immunotherapy Response In Stage IV Lung Cancer With Brain Metastasis

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Figure 1. Brain MRI at diagnosis and last Brain MRI performed. The image shows a temporal metastatic lesion at diagnosis (A) and last Brain MRI with maintained complete response (B), in postcontrast 3D T1-weighted.

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Credit: 2024 Costa and Magalhães

"In the last decade, immunotherapy agents changed the treatment landscape for Non-Small Cell Lung Cancer (NSCLC)."

BUFFALO, NY - October 18, 2024 – A new case report was published in Oncoscience (Volume 11) on October 8, 2024, entitled, "Complete and long-lasting response to immunotherapy in a stage IV non-small cell lung cancer with brain metastasis."

As highlighted in the abstract of this report, approximately 20% of lung cancer patients have brain metastases at diagnosis, which is associated with a worse prognosis and negatively impacts quality of life. The emergence of new systemic treatment options, such as immune checkpoint inhibitors (ICI) and targeted therapies, has changed the prognosis for stage IV lung cancer patients. However, the impact of treatment sequencing—both local and systemic—in patients with stage IV lung cancer and brain metastases remains unclear.

Researchers Mafalda Costa and Helena Magalhães from the Department of Medical Oncology, Hospital Pedro Hispano in Matosinhos, Portugal present the case of a 51-year-old man diagnosed with stage IV non-small cell lung cancer (NSCLC) and brain metastasis. After undergoing whole brain radiotherapy (WBRT), the patient achieved both intracranial and extracranial complete response following second-line treatment with an immune checkpoint inhibitor. Currently, he has an overall survival of 87 months and a progression-free survival of 73 months, maintaining an optimal quality of life.

"We hypothesized that treatment sequencing of WBRT and immunotherapy could explain this unexpected outcome."

Continue reading: DOI: https://doi.Org/10.18632/oncoscience.609 

Corresponding author: Mafalda Costa - mafalda.Teixeiracosta@ulsm.Min-saude.Pt

Keywords: cancer, lung cancer, complete response, immune checkpoint inhibitors, brain metastasis, whole-brain radiotherapy

About Oncoscience: 

Oncoscience is a peer-reviewed, open-access, traditional journal covering the rapidly growing field of cancer research, especially emergent topics not currently covered by other journals. This journal has a special mission: Freeing oncology from publication cost. It is free for the readers and the authors.

Oncoscience is indexed and archived by PubMed, PubMed Central, Scopus, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Method of Research

Case study

Subject of Research

Not applicable

Article Title

Complete and long-lasting response to immunotherapy in a stage IV non-small cell lung cancer with brain metastasis

Article Publication Date

8-Oct-2024

COI Statement

Authors have no conflicts of interest to declare.

Disclaimer: AAAS and EurekAlert! Are not responsible for the accuracy of news releases posted to EurekAlert! By contributing institutions or for the use of any information through the EurekAlert system.

ASTRO: Many Patients Have Cognitive Recovery After Brain Radiation Therapy

(HealthDay News) — Many patients with brain metastases who experience initial neurocognitive failure (NCF) following brain radiation therapy demonstrate recovery, with greater rates of cognitive recovery (CR) for stereotactic radiosurgery (SRS), according to a study presented at the annual meeting of the American Society for Radiation Oncology, held from Sept. 29 to Oct. 2 in Washington, DC.

Hua Ren Ryan Cherng, MD, from the University of Maryland Medical Center in Baltimore, and colleagues examined CR following initial NCF in patients treated with SRS and whole brain radiation therapy (WBRT) in a pooled analysis of three phase 3 randomized clinical trials. The analyses included 288 patients with trial-defined NCF.

The researchers found that the pooled cumulative incidence of full CR was 38% and 42%  at 6 and 12 months after NCF onset, respectively. At the same time points, the incidence rates of improvement on any previously failed cognitive test were 73% and 76%, respectively. The cumulative incidence of full CR was significantly higher with postoperative SRS versus WBRT and for SRS alone versus SRS + WBRT (hazard ratios, 2.68 and 2.35, respectively). A trend toward a higher incidence of CR was seen for hippocampal-avoidance-WBRT versus WBRT. No difference was seen in the rates of improvement in cognitive tests based on treatment. Compared with WBRT, SRS was predictive of CR in a multivariable pooled analysis (hazard ratio, 2.42).

"Our research finds that the cognitive side effects of radiation treatment for people with brain metastases appear to be fully reversible, and patients appear to be able to sustain that recovery over the long term," Cherng said in a statement.

Several authors disclosed ties to the biopharmaceutical industry.

References:

People who experience side effects from cranial radiation therapy may recover full neurocognitive function within months. News release. ASTRO; September 29, 2024.

Neurocognitive Side Effects Of Brain Radiation Subside For Many, Analysis Shows

Patients with brain metastases who experienced cognitive side effects following radiation therapy often fully regain cognitive function, according to a pooled analysis of three phase III trials.

Of 288 patients who experienced neurocognitive failure after treatment, the pooled cumulative incidence of full cognitive recovery was about 38% at 6 months and 42% at 12 months, reported Hua-Ren Ryan Cherng, MD, of the University of Maryland Medical Center in Baltimore.

"Our analysis reveals that a sizeable proportion of patients experience full neurocognitive function failure reversal," said Cherng during a session at the American Society for Radiation Oncology annual meeting in Washington, D.C. Considering the sensitivity of tests evaluating cognition, "clinically meaningful improvements in cognition are probably higher than 40%," he added.

The findings may help counsel patients about their likelihood of meaningful cognitive improvement after radiation and underscore that neurocognitive decline is not necessarily permanent, which "has potential implications for how we think about and design clinical trials moving forward," Cherng suggested.

During a press briefing at which Cherng presented the study's results, discussant Lia Halasz, MD, of the University of Washington and Fred Hutchinson Cancer Center in Seattle, noted that radiation therapy "understandably ... Does come with some cognitive decreases, and this is very concerning to people. We all know ... Anecdotally that a lot of times this does pass. But we didn't necessarily always have the data on how often it does."

"I'm excited about this analysis because it took three cooperative group trials with many patients who were randomized to different types of radiation therapy to really figure out what is better in terms of cognitive outcomes," she said. "I think an analysis such as this I can bring into my clinic and really help our patients understand what they may go through."

The three randomized trials included in the analysis were NCCTG N107C/CEC.3, which compared postoperative stereotactic radiosurgery (SRS) versus whole-brain radiation therapy (WBRT) for patients with resected metastatic brain disease; NCCTG N0574, which compared SRS versus SRS plus WBRT for patients with one to three brain metastases; and NRG Oncology CC001, which compared hippocampal-avoidance WBRT plus memantine versus WBRT plus memantine for patients with brain metastases.

"The way in which these trials were set up, once you met the definition of cognitive failure you met the endpoint of the trial," Cherng explained. "But the researchers continued to collect longitudinal testing data for these patients, so this is specifically an analysis looking at those patients who had longitudinal testing data beyond their time point of cognitive failure on these trials."

Patients in the studies underwent a batch of cognitive tests administered before treatment and again at 6 and 12 months. Full cognitive recovery was defined as no longer exhibiting a ≥1 standard deviation (SD) decline from baseline on any cognitive test, while recovery on individual tests was defined as at least a 1-SD improvement on a previously failed test.

Longer longitudinal cognitive testing data beyond 12 months was available for 65 patients in these trials, and showed that about two-thirds were able to sustain cognitive recovery and had no evidence of neurocognitive toxicity.

When looking at cognitive recovery by trial, the cumulative incidence of full cognitive recovery was significantly greater among patients who received SRS versus WBRT in the NCCTG N107C/CEC.3 and NCCTG N0574 trials (HR 2.42, 95% CI 1.70-3.45, P<0.0001).

There was also a trend toward an increase in the cumulative incidence of full cognitive recovery among patients who received hippocampal-avoidance WBRT versus WBRT alone in the NRG Oncology CC001 trial (HR 1.56, 95% CI 0.98-2.48, P=0.061).

During a Q&A period, Cherng was asked about disease control in these patients in the context of weighing the potential benefit of therapy with its impact on cognition and quality of life.

"That is always something we are considering -- how to balance neurocognitive outcomes versus intracranial brain control," Cherng said. "Those data are reported in the primary manuscripts of these trials, but ... Distant brain control is always worse with more of a focal SRS approach as opposed to whole-brain radiation."

Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

Cherng had no disclosures.

Halasz reported relationships with BioMimetix and UpToDate.

Primary Source

American Society for Radiation Oncology

Source Reference: Cherng HRR, et al "Evaluating neurocognitive recovery following stereotactic radiosurgery and whole brain radiation therapy: insights from a pooled analysis of three phase III trials" ASTRO 2024; Abstract 150.

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