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Timothy R. Smith, Rohan R. Lall, Rishi R. Lall, Isaac Josh Abecassis, Omar M. Arnaout, MaryAnne H. Marymont, Kristin R. Swanson, and James P. Chandler

Object

Patients with systemic cancer and a single brain metastasis who undergo treatment with resection plus radiotherapy live longer and have a better quality of life than those treated with radiotherapy alone. Historically, whole-brain radiotherapy (WBRT) has been the mainstay of radiation therapy; however, it is associated with significant delayed neurocognitive sequelae. In this study, the authors looked at survival in patients with single and multiple intracranial metastases who had undergone surgery and adjuvant stereotactic radiosurgery (SRS) to the tumor bed and synchronous lesions.

Methods

The authors retrospectively reviewed the records from an 8-year period at a single institution for consecutive patients with brain metastases treated via complete resection of dominant lesions and adjuvant radiosurgery. The cohort was analyzed for time to local progression, synchronous lesion progression, new intracranial lesion development, systemic progression, and overall survival. The Kaplan-Meier method (stratified by age, sex, tumor histology, and number of intracranial lesions prior to surgery) was used to calculate both progression-free and overall survival. A Cox proportional-hazards regression model was also fitted with the number of intracranial lesions as the predictor and survival as the outcome controlling for disease severity, age, sex, and primary histology.

Results

The median overall follow-up among the 150-person cohort eligible for analysis was 17 months. Patients had an average age of 46.2 years (range 16–82 years), and 62.7% were female. The mean (± standard deviation) number of intracranial lesions per patient was 2.5 ± 2.3. The mean time between surgery and stereotactic radiosurgery (SRS) was 3.2 ± 4.1 weeks. Primary cancers included lung cancer (43.3%), breast cancer (21.3%), melanoma (10.0%), renal cell carcinoma (6.7%), and colon cancer (6.7%). The average number of isocenters per treated lesion was 7.6 ± 6.6, and the average treatment dose was 17.8 ± 2.8 Gy. One-year survival for patients in this cohort was 52%, and the 1-year local control rate was 77%. The median (±standard error) overall survival was 13.2 ± 1.9 months. There was no difference in survival between patients with a single lesion and those with multiple lesions (p = 0.319) after controlling for age, sex, and histology of primary tumor. Patients with primary breast histology had the greatest overall median survival (22.9 ± 6.2 months); patients with colorectal cancer had the shortest overall median survival (5.3 ± 1.8 months). The most common cause of death in this series was systemic progression (79%).

Conclusions

These results confirm that 1-year survival for patients with multiple intracranial metastases treated with resection followed by SRS to both the tumor bed and synchronous lesions is similar to established outcomes for patients with a single intracranial metastasis.

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Shashwat Tripathi, Tito Vivas-Buitrago, Ricardo A. Domingo, Gaetano De Biase, Desmond Brown, Oluwaseun O. Akinduro, Andres Ramos-Fresnedo, Wendy Sherman, Vivek Gupta, Erik H. Middlebrooks, David S. Sabsevitz, Alyx B. Porter, Joon H. Uhm, Bernard R. Bendok, Ian Parney, Fredric B. Meyer, Kaisorn L. Chaichana, Kristin R. Swanson, and Alfredo Quiñones-Hinojosa

OBJECTIVE

Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH–wild-type glioblastoma (GBM) to further improve patients’ overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH–wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile).

METHODS

Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3 × (6.106/[VT2 1/1 − VT1 1/1])2, where VT2 and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse.

RESULTS

A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98–0.99; p = 0.02; and HR 0.98, 95% CI 0.96–0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively.

CONCLUSIONS

The impact of SMR on OS for patients with IDH–wild-type GBM is influenced by the degree of tumor invasiveness. The authors’ results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH–wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.