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Shota Tanaka, Fredric B. Meyer, Jan C. Buckner, Joon H. Uhm, Elizabeth S. Yan, and Ian F. Parney

Object

Optimum management for elderly patients with newly diagnosed glioblastoma (GBM) in the temozolomide (TMZ) era is not well defined. The object of this study was to clarify outcomes in this population.

Methods

The authors retrospectively reviewed 105 consecutive cases involving elderly patients (age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008.

Results

The patients' median age was 74 years (range 66–87 years), and the median Karnofsky Performance Status (KPS) score was 80 (range 40–90). Half of the patients underwent biopsy and half underwent resection. Patients with deep-seated lesions (19 patients [18%]) or multifocal lesions (34 patients [32%]) were more likely to have biopsy than resection (p = 0.0001 and 0.0009, respectively). New persistent neurological deficits developed in 7 patients (6.7%). Postoperative hemorrhage occurred in 6 patients (5.7%), all of whom underwent biopsy. Complete follow-up data regarding adjuvant treatment was available in 84 patients. Forty-one (49%) were treated with chemotherapy (mostly TMZ) and radiation therapy (RT), and 23 (27%) with RT alone. Nineteen (23%) received only palliative care after surgery (more common with biopsy, p = 0.03). Chemotherapy complications occurred in 28.6% (Grade 3 or 4 hematological complications in 11.9%). The median values for progression-free survival (PFS) and overall survival (OS) were 3.5 and 5.5 months. In a multivariate analysis, younger age (p = 0.03, risk ratio [RR] 0.34, 95% CI 0.13–0.89), single lesion (p = 0.02, RR 0.51, 95% CI 0.30–0.89), resection (p = 0.04, RR 0.54, 95% CI 0.31–0.94), and adjuvant treatment (p = 0.0001, RR 0.24, 95% CI 0.11–0.49) were associated with better OS. Only adjuvant treatment was significantly associated with prolonged PFS (p = 0.0007, RR 0.27, 95% CI 0.13–0.57). With combined therapy with resection, RT, and chemotherapy, the median PFS and OS were 8 and 12.5 months, respectively.

Conclusions

The prognosis for GBM worsens with increasing age in elderly patients. With important risks, resection and adjuvant treatment are associated with prolonged survival. Although selection bias cannot be excluded in this retrospective study, advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.

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Benjamin T. Himes, Michael W. Ruff, Jaimie J. Van Gompel, Sean S. Park, Evanthia Galanis, Timothy J. Kaufmann, and Joon H. Uhm

The authors present the case of a man with a papillary craniopharyngioma, first diagnosed at 47 years of age, who experienced multiple recurrences. Review of the pathologic specimen from his first resection demonstrated the BRAF V600E mutation. With his most recent recurrence following previous surgery and radiotherapy, at 52 years of age, the decision was made to initiate treatment with the BRAF V600E inhibitor dabrafenib. Imaging following initiation of dabrafenib demonstrated reduction in tumor size. He remained on dabrafenib therapy for approximately 1 year and continued to demonstrate a good clinical result. At that time the decision was made to discontinue dabrafenib therapy and follow up with serial imaging. After more than 1 year of follow-up since stopping dabrafenib, the patient has continued to do well with no radiographic evidence of tumor progression and continues to be monitored with frequent interval imaging.

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Benjamin T. Himes, Michael W. Ruff, Jaimie J. Van Gompel, Sean S. Park, Evanthia Galanis, Timothy J. Kaufmann, and Joon H. Uhm

The authors present the case of a man with a papillary craniopharyngioma, first diagnosed at 47 years of age, who experienced multiple recurrences. Review of the pathologic specimen from his first resection demonstrated the BRAF V600E mutation. With his most recent recurrence following previous surgery and radiotherapy, at 52 years of age, the decision was made to initiate treatment with the BRAF V600E inhibitor dabrafenib. Imaging following initiation of dabrafenib demonstrated reduction in tumor size. He remained on dabrafenib therapy for approximately 1 year and continued to demonstrate a good clinical result. At that time the decision was made to discontinue dabrafenib therapy and follow up with serial imaging. After more than 1 year of follow-up since stopping dabrafenib, the patient has continued to do well with no radiographic evidence of tumor progression and continues to be monitored with frequent interval imaging.

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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.