Pseudoprogression versus true progression in glioblastoma: what neurosurgeons need to know

J Neurosurg 139:748–759, 2023

Management of patients with glioblastoma (GBM) is complex and involves implementing standard therapies including resection, radiation therapy, and chemotherapy, as well as novel immunotherapies and targeted small-molecule inhibitors through clinical trials and precision medicine approaches. As treatments have advanced, the radiological and clinical assessment of patients with GBM has become even more challenging and nuanced.

Advances in spatial resolution and both anatomical and physiological information that can be derived from MRI have greatly improved the noninvasive assessment of GBM before, during, and after therapy.

Identification of pseudoprogression (PsP), defined as changes concerning for tumor progression that are, in fact, transient and related to treatment response, is critical for successful patient management. These temporary changes can produce new clinical symptoms due to mass effect and edema. Differentiating this entity from true tumor progression is a major decision point in the patient’s management and prognosis.

Providers may choose to start an alternative therapy, transition to a clinical trial, consider repeat resection, or continue with the current therapy in hopes of resolution. In this review, the authors describe the invasive and noninvasive techniques neurosurgeons need to be aware of to identify PsP and facilitate surgical decision-making.

Risk of Tract Seeding Following Laser Interstitial Thermal Therapy for Brain Tumors

Neurosurgery 93:198–205, 2023

The management of intracranial oncological disease remains a significant challenge despite advances in systemic cancer therapy. Laser interstitial thermal therapy (LITT) represents a novel treatment for local control of brain tumors through photocoagulation with a stereotactically implanted laser fiber. Because the use of laser interstitial thermal therapy continues to increase within neurosurgery, characterization of LITT is necessary to improve outcomes.

OBJECTIVE: To quantify the risk of tumor seeding along the laser fiber tract in patients receiving LITT for primary or metastatic brain tumors at a high-volume treatment center.

METHODS: We retrospectively reviewed all patients receiving LITT from 2015 to 2021 at our medical center. Patients with biopsy-confirmed tumors were included in this study. Tract seeding was identified as discontinuous, newly enhancing tumor along the LITT tract.

RESULTS: Fifty-six patients received LITT for biopsy-confirmed tumors from 2015 to 2021, with tract seeding identified in 3 (5.4%). Twenty-nine (51.8%) patients had gliomas, while the remainder had metastases, of which lung was the most common histology (20 patients, 74%). Tract seeding was associated with ablation proceeding inward from superficial tumor margin closest to the cranial entry point (P = .03). Patients with tract seeding had a shorter median time to progression of 1.1 (0.1-1.3) months vs 4.2 (2.2-8.6) months (P = .03).

CONCLUSION: Although the risk of tract seeding after LITT is reassuringly low, it is associated with decreased progression-free survival. This risk may be related to surgical technique or experience. Follow-up radiosurgery to the LITT tract has the potential to prevent this complication.

Predictors of Local Control of Brain Metastasis TreatedWith Laser Interstitial Thermal Therapy

Neurosurgery 87:112–122, 2020

Laser Interstitial Thermal Therapy (LITT) has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS.

OBJECTIVE: To evaluate the predictive factors associated with local recurrence after LITT.

METHODS: Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence.

RESULTS: A total of 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence, and 31 radiation necrosis). Freedom from local recurrence at 6 mo was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 mo. Incompletely ablated lesions had a shorter median time for local recurrence (P < .001). Larger lesions (>6 cc) had shorter time for local recurrence (P = .03). Dural-based lesions showed a shorter time to local recurrence (P = .01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (P = .01). Patients receiving systemic therapy after LITT had longer time to local recurrence (P = .01). In multivariate Cox-regression model, the HR for incomplete ablated lesions was 4.88 (P < .001), 3.12 (P = .03) for recurrent tumors, and 2.56 (P = .02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%.

CONCLUSION: Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.

 

Using Higher Isodose Lines for Gamma Knife Treatment of 1 to 3 Brain Metastases Is Safe and Effective

Motor function after stereotactic radiosurgery for brain metastases in the region of the motor cortex

Neurosurgery 74:360–366, 2014

Higher isodose lines (IDLs) in Gamma Knife (GK) Perfexion treatment of brain metastases (BMet) could result in lower local control (LC) or higher radiation necrosis (RN) rates, but reduce treatment time.

OBJECTIVE: To assess the impact of the heterogeneity index (HI) and conformality index (CFI) on local failure (LF) for patients treated with GK for 1 to 3 BMet.

METHODS: From an institutional review board—approved database, 320 patients with 496 BMet were identified, treated for 1 to 3 BMet from July 2007 to April 2011 on GK Perfexion. Cox proportional hazards regression was used to analyze significance of HI, CFI, IDL, dose, tumor diameter, recursive partitioning analysis class, tumor radioresistance, primary, smoking history, metastasis location, and whole-brain radiation therapy (WBRT) history with LF and RN.

RESULTS: Median follow-up by lesion was 6.8 months (range, 0-49.6). The series median survival was 14.2 months. Per RECIST, 9.5% of lesions failed, 33.9% were stable, 38.3% partially responded, 17.1% responded completely, and 1.2% could not be assessed. The 12-month LC rate was 87.3%. On univariate analysis, a dose less than 20 Gy (hazard ratio [HR]: 2.940, P , .001); tumor size (HR: 1.674, P , .001); and cerebellum/brainstem location vs other (HR: 1.891, P = .043) were significant for LF. Non-small cell lung cancer (HR: 0.333, P = .0097) was associated with better LC. On multivariate analysis, tumor size (HR: 1.696, P , .001) and cerebellum/brainstem location vs other (HR: 1.959, P = .033) remained significant for LF. Variables not significant for LF included CI, IDL, and HI.

CONCLUSION: Our study of patients with 1 to 3 BMet treated with GK demonstrated no difference in LC or RN with varying HI, indicating that physicians can treat to IDL at 70% or higher IDL to reduce treatment time without increased LF or RN.

Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality?

Radiation necrosis

J Neurooncol (2013) 112:141–152

Differentiating post radiation necrosis from progression of glioma and pseudoprogression poses a diagnostic conundrum for many clinicians. As radiation therapy and temozolomide chemotherapy have become the mainstay of treatment for higher-grade gliomas, radiation necrosis and post treatment changes such as pseudoprogression have become a more relevant clinical problem for neurosurgeons and neurooncologists. Due to their radiological similarity to tumor progression, accurate recognition of these findings remains paramount given their vastly different treatment regimens and prognoses. However, no consensus has been reached on the optimal technique to discriminate between these two lesions.

In order to clarify the types of imaging modalities for recurrent enhancing lesions, we conducted a systematic review of case reports, case series, and prospective studies to increase our current understanding of the imaging options for these common lesions and their efficacy. In particular, we were interested in distinguishing radiation necrosis from true tumor progression. A PubMed search was performed to include all relevant studies where the imaging was used to differentiate between radiation necrosis and recurrent gliomas with post-radiation enhancing lesions.

After screening for certain parameters in our study, seventeen articles with 435 patients were included in our analysis including 10 retrospective and 7 prospective studies. The average time from the end of radiation therapy to the onset of a recurrent enhancing lesion was 13.2 months. The most sensitive and specific imaging modality was SPECT with a sensitivity of 87.6 % and specificity of 97.8 %.

Based on our review, we conclude that certain imaging modalities may be preferred over other less sensitive/specific techniques. Overall, tests such as SPECT may be preferable in differentiating TP (tumor progression) from RN (radiation necrosis) due to its high specificity, while nonspecific imaging such as conventional MRI is not ideal.