Category: Radiation Therapy

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Early Initiation of Radiation Therapy Improves Survival in Elderly Patients With Glioblastoma

Neurosurgery 98:1402–1412, 2026

This clinical study evaluates the effect of early postoperative radiation therapy (RT) initiation on survival in patients aged 65 and older with IDH‑wildtype glioblastoma, analyzing outcomes from a prospective registry of 56 patients treated between 2020–2024. Survival analyses, including Kaplan‑Meier curves and Cox regression, compare outcomes for RT started <20 days versus ≥20 days after surgery and examine RT fractionation and temozolomide use.

Results show that initiating RT within 20 days post‑surgery is associated with improved overall survival and progression‑free survival on univariate analysis, while multivariate models indicate confounding by performance status and adjuvant temozolomide; adjuvant TMZ remains a strong positive predictor of survival. The authors conclude early RT may benefit elderly GBM patients and call for prospective randomized trials to confirm timing effects.

Study aim: Evaluate whether earlier start of postoperative radiation therapy (RT) improves survival in elderly (≥65) patients with newly diagnosed IDH-wildtype glioblastoma.

Cohort & design: Retrospective cohort using a prospective registry (2020–2024), 56 patients, comparing RT start <20 days vs ≥20 days after surgery; endpoints were overall survival (OS) and progression-free survival (PFS).

Univariate survival finding: Starting RT <20 days after surgery was associated with improved OS (P=.0460) and PFS (P=.0075) versus ≥20 days.

Adjusted (multivariate) finding: After adjustment (including KPS and adjuvant temozolomide), RT timing was not statistically significant for OS (P=.2962) or PFS (P=.0670), indicating likely confounding.

Temozolomide effect: Adjuvant temozolomide was a significant predictor of better outcomes on multivariate analysis for both OS (P=.0038; HR 0.16) and PFS (P=.0133; HR 0.27).

Fractionation nuance: Among those starting RT early (<20 days), conventionally fractionated RT (60 Gy/30 fx) showed significantly improved PFS (P=.0164), while hypofractionated RT (40 Gy/15 fx) did not reach significance (P=.0509).

Baseline group differences: The <20-day RT group had better performance status (higher KPS, lower ECOG) and higher rates of receiving adjuvant temozolomide, which may influence observed survival differences.

Clinical implication noted: Timely initiation of adjuvant therapy (RT and chemotherapy) may be particularly important in elderly patients, but stronger evidence (e.g., prospective randomized trial) is needed to define optimal timing and account for confounding/logistical delays.

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Longitudinal brain volumetrics in glioma survivors

J Neurosurg 141:634–641, 2024

Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT.

METHODS This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models.

RESULTS The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36–18.9 years), and the median number of time points analyzed per patient was 12 (range 2–40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (β = −0.06, p < 0.001) and use of RT (β = −1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (β = −0.08, p < 0.001), midline involvement (β = 1.31, p = 0.006), and use of RT (β = −1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (β = −0.0027, p = 0.001), tumor resection (β = −0.069, p < 0.001), use of chemotherapy (β = −0.0597, p = 0.003), and use of RT (β = −0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model.

CONCLUSIONS This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

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Risk factors associated with postoperative recurrence in atypical intracranial meningioma

Acta Neurochirurgica (2019) 161:2563–2570

Atypical meningioma (AM) has a high rate of local recurrence after surgery, and the role of adjuvant radiotherapy in AM remains controversial. We analysed progression-free survival (PFS) and identified the factors associated with postoperative recurrence in AM patients.

Methods Data were obtained from 263 AM patients who underwent surgery at our institution between October 2009 and September 2018. Analyses included factors such as the extent of surgical resection, MIB-1 labelling index, brain invasion and therapy modality. Univariate and multivariate analyses were used to assess recurrence-related prognostic factors.

Result The median follow-up duration was 41 months, and the median PFS was 28 months. Gross total resection (GTR) was achieved in 213 (81.0%) patients, and 86 (32.7%) patients received postoperative radiation therapy (RT). During follow-up, there were 61 (23.2%) tumour recurrences. In a Cox multivariate analysis, MIB-1 labelling index (hazard ratio = 2.637; p < 0.001), secondary tumour (hazard ratio = 3.541; p < 0.001), tumour size (hazard ratio = 1.818; p = 0.032) and extent of resection (hazard ratio = 2.861; p < 0.001) were independent significant predictors of tumour recurrence. RTwas associated with reduced tumour recurrence in subtotal resection (STR) (p = 0.023) but not GTR (p = 0.923). An analysis of 6 meningioma patients who underwent more than 3 operations suggested that the recurrence time became shorter and the MIB-1 labelling index increased as the number of recurrences increased.

Conclusions MIB-1 labelling index, secondary tumour, tumour size and extent of resection were powerful predictors of recurrence in AM patients. Postoperative RT did not decrease the risk of recurrence in GTR patients.

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Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases

Neurosurgery, Volume 85, Issue 2, August 2019, Pages 257–263

The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial.

OBJECTIVE: To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group.

METHODS: A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan–Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox propor- tional hazards.

RESULTS: Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respec- tively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume param- eters predicted for death, neurologic death or toxicity.

CONCLUSION: SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

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Gamma Knife stereotactic radiosurgery for cavernous sinus meningioma: long-term follow-up in 200 patients

J Neurosurg 130:1799–1808, 2019

The authors of this study evaluate the long-term outcomes of stereotactic radiosurgery (SRS) for cavernous sinus meningioma (CSM).

METHODS The authors retrospectively assessed treatment outcomes 5–18 years after SRS in 200 patients with CSM. The median patient age was 57 years (range 22–83 years). In total, 120 (60%) patients underwent Gamma Knife SRS as primary management, 46 (23%) for residual tumors, and 34 (17%) for recurrent tumors after one or more surgical procedures. The median tumor target volume was 7.5 cm3 (range 0.1–37.3 cm3), and the median margin dose was 13.0 Gy (range 10–20 Gy).

RESULTS Tumor volume regressed in 121 (61%) patients, was unchanged in 49 (25%), and increased over time in 30 (15%) during a median imaging follow-up of 101 months. Actuarial tumor control rates at the 5-, 10-, and 15-year followups were 92%, 84%, and 75%, respectively. Of the 120 patients who had undergone SRS as a primary treatment (primary SRS), tumor progression was observed in 14 (11.7%) patients at a median of 48.9 months (range 4.8–120.0 months) after SRS, and actuarial tumor control rates were 98%, 93%, 85%, and 85% at the 1-, 5-, 10-, and 15-year follow-ups post-SRS. A history of tumor progression after microsurgery was an independent predictor of an unfavorable response to radiosurgery (p = 0.009, HR = 4.161, 95% CI 1.438–12.045). Forty-four (26%) of 170 patients who had presented with at least one cranial nerve (CN) deficit improved after SRS. Development of new CN deficits after initial microsurgical resection was an unfavorable factor for improvement after SRS (p = 0.014, HR = 0.169, 95% CI 0.041–0.702). Fifteen (7.5%) patients experienced permanent CN deficits without evidence of tumor progression at a median onset of 9 months (range 2.3–85 months) after SRS. Patients with larger tumor volumes (≥ 10 cm3) were more likely to develop permanent CN complications (p = 0.046, HR = 3.629, 95% CI 1.026–12.838). Three patients (1.5%) developed delayed pituitary dysfunction after SRS.

CONCLUSIONS This long-term study showed that Gamma Knife radiosurgery provided long-term tumor control for most patients with CSM. Patients who underwent SRS for progressive tumors after prior microsurgery had a greater chance of tumor growth than the patients without prior surgery or those with residual tumor treated after microsurgery.

 

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The Promise of Proton Therapy for Central Nervous System Malignancies

Neurosurgery, Volume 84, Issue 5, May 2019, Pages 1000–1010

Radiation therapy plays a significant role in management of benign and malignant diseases of the central nervous system. Patients may be at risk of acute and late toxicity from radiation therapy due to dose deposition in critical normal structures.

In contrast to conventional photon delivery techniques, proton therapy is characterized by Bragg peak dose deposition which results in decreased exit dose beyond the target and greater sparing of normal structure which may reduce the rate of late toxicities from treatment. Dosimetric studies have demonstrated reduced dose to normal structures using proton therapy as compared to photon therapy. In addition, clinical studies are being reported demonstrating safety, feasibility, and low rates of acute toxicity.

Technical challenges in proton therapy remain, including full understanding of depth of proton penetration and the biological activity in the distal Bragg peak. In addition, longer clinical followup is required to demonstrate reduction in late toxicities as compared to conventional photon-based radiation techniques.

In this review, we summarize the current clinical literature and areas of active investigation in proton therapy for adult central nervous system malignancies.

 

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