Clinical Features, Survival and Prognostic Factors of Glycogen-Rich Clear Cell Carcinoma (GRCC) of the Breast in the U.S. Population

The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical associations have been inconsistent due to reliance on case reports and limited case series. As a result, the prognostic implication of this cancer subtype remains unclear. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) program database, we compared the incidence, demographics and prognostic factors of 155 cases of GRCC of the breast to 1,251,584 cases of other (non-GRCC) breast carcinomas. We demonstrate that GRCC is more likely to be identified as high grade, advanced stage, and more likely to have triple negative receptor status. GRCC cases display a poorer prognosis than non-GRCC carcinomas of the breast irrespective of age, AJCC staging, tumor grade, joint hormone receptor/human epidermal growth factor receptor 2 (HER2) status, and treatment. Similar to non-GRCC carcinomas, older age and higher American Joint Committee on Cancer (AJCC)/TNM staging were associated with poorer prognosis for GRCC, while treatment with surgery and radiation were associated with improved survival. Radiation, specifically in the setting of breast-conserving surgery, further improved survival compared to surgery alone. Our study highlights the poorer prognosis associated with glycogen accumulation in breast cancers and hence stresses the importance of identifying this more aggressive tumor type

Clinical Features, Survival and Prognostic Factors of Glycogen-Rich Clear Cell Carcinoma (GRCC) of the Breast in the U.S. Population

The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical associations have been inconsistent due to reliance on case reports and limited case series. As a result, the prognostic implication of this cancer subtype remains unclear. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) program database, we compared the incidence, demographics and prognostic factors of 155 cases of GRCC of the breast to 1,251,584 cases of other (non-GRCC) breast carcinomas. We demonstrate that GRCC is more likely to be identified as high grade, advanced stage, and more likely to have triple negative receptor status. GRCC cases display a poorer prognosis than non-GRCC carcinomas of the breast irrespective of age, AJCC staging, tumor grade, joint hormone receptor/human epidermal growth factor receptor 2 (HER2) status, and treatment. Similar to non-GRCC carcinomas, older age and higher American Joint Committee on Cancer (AJCC)/TNM staging were associated with poorer prognosis for GRCC, while treatment with surgery and radiation were associated with improved survival. Radiation, specifically in the setting of breast-conserving surgery, further improved survival compared to surgery alone. Our study highlights the poorer prognosis associated with glycogen accumulation in breast cancers and hence stresses the importance of identifying this more aggressive tumor type

Risk Stratification for Management of Solitary Fibrous Tumor/Hemangiopericytoma of the Central Nervous System

Introduction: Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) of the central nervous system (CNS) is a rare meningeal tumor. Given the absence of prospective or randomized data, there are no standard indications for radiotherapy. Recently, the NRG Oncology and EORTC cooperative groups successfully accrued and completed the first prospective trials evaluating risk-adapted adjuvant radiotherapy strategies for meningiomas. Using a similar framework, we sought to develop prognostic risk categories that may predict the survival benefit associated with radiotherapy, using two large national datasets. Methods: We queried the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) databases for all newly diagnosed cases of SFT/HPC within the CNS. Risk categories were created, as follows: low risk—grade 1, with any extent of resection (EOR) and grade 2, with gross–total resection; intermediate risk—grade 2, with biopsy/subtotal resection; high risk—grade 3 with any EOR. The Kaplan–Meier method and Cox proportional hazards regressions were used to determine the association of risk categories with overall and cause-specific survival. We then determined the association of radiotherapy with overall survival in the NCDB, stratified by risk group. Results: We identified 866 and 683 patients from the NCDB and SEER databases who were evaluated, respectively. In the NCDB, the 75% survival times for low- (n = 312), intermediate- (n = 239), and high-risk (n = 315) patients were not reached, 86 months (HR 1.60 (95% CI 1.01–2.55)), and 55 months (HR 2.56 (95% CI 1.68–3.89)), respectively. Our risk categories were validated for overall and cause-specific survival in the SEER dataset. Radiotherapy was associated with improved survival in the high- (HR 0.46 (0.29–0.74)) and intermediate-risk groups (HR 0.52 (0.27–0.99)) but not in the low-risk group (HR 1.26 (0.60–2.65)). The association of radiotherapy with overall survival remained significant in the multivariable analysis for the high-risk group (HR 0.55 (0.34–0.89)) but not for the intermediate-risk group (HR 0.74 (0.38–1.47)). Similar results were observed in a time-dependent landmark sensitivity analysis. Conclusion: Risk stratification based on grade and EOR is prognostic of overall and cause-specific survival for SFT/HPCs of the CNS and performs better than any individual clinical factor. These risk categories appear to predict the survival benefit from radiotherapy, which is limited to the high-risk group and, potentially, the intermediate-risk group. These data may serve as the basis for a prospective study evaluating the management of meningeal SFT/HPCs

Risk Stratification for Management of Solitary Fibrous Tumor/Hemangiopericytoma of the Central Nervous System

Introduction: Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) of the central nervous system (CNS) is a rare meningeal tumor. Given the absence of prospective or randomized data, there are no standard indications for radiotherapy. Recently, the NRG Oncology and EORTC cooperative groups successfully accrued and completed the first prospective trials evaluating risk-adapted adjuvant radiotherapy strategies for meningiomas. Using a similar framework, we sought to develop prognostic risk categories that may predict the survival benefit associated with radiotherapy, using two large national datasets. Methods: We queried the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) databases for all newly diagnosed cases of SFT/HPC within the CNS. Risk categories were created, as follows: low risk—grade 1, with any extent of resection (EOR) and grade 2, with gross–total resection; intermediate risk—grade 2, with biopsy/subtotal resection; high risk—grade 3 with any EOR. The Kaplan–Meier method and Cox proportional hazards regressions were used to determine the association of risk categories with overall and cause-specific survival. We then determined the association of radiotherapy with overall survival in the NCDB, stratified by risk group. Results: We identified 866 and 683 patients from the NCDB and SEER databases who were evaluated, respectively. In the NCDB, the 75% survival times for low- (n = 312), intermediate- (n = 239), and high-risk (n = 315) patients were not reached, 86 months (HR 1.60 (95% CI 1.01–2.55)), and 55 months (HR 2.56 (95% CI 1.68–3.89)), respectively. Our risk categories were validated for overall and cause-specific survival in the SEER dataset. Radiotherapy was associated with improved survival in the high- (HR 0.46 (0.29–0.74)) and intermediate-risk groups (HR 0.52 (0.27–0.99)) but not in the low-risk group (HR 1.26 (0.60–2.65)). The association of radiotherapy with overall survival remained significant in the multivariable analysis for the high-risk group (HR 0.55 (0.34–0.89)) but not for the intermediate-risk group (HR 0.74 (0.38–1.47)). Similar results were observed in a time-dependent landmark sensitivity analysis. Conclusion: Risk stratification based on grade and EOR is prognostic of overall and cause-specific survival for SFT/HPCs of the CNS and performs better than any individual clinical factor. These risk categories appear to predict the survival benefit from radiotherapy, which is limited to the high-risk group and, potentially, the intermediate-risk group. These data may serve as the basis for a prospective study evaluating the management of meningeal SFT/HPCs

Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas: A Multicenter Study (STORM)

The role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM, a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas. Data on patients with recurrent grade 2 and 3 meningioma treated with SRS at first recurrence were retrospectively collected from eight academic centers in the United States. Patients with multiple lesions at the time of initial diagnosis or more than two lesions at the time of first recurrence were excluded from this analysis. Patient demographics and treatment parameters were extracted at time of diagnosis, first recurrence, and second recurrence. Oncologic outcomes including progression-free survival (PFS) and overall survival (OS) as well as toxicity outcomes were reported at the patient level. From 2000-2022, 108 patients were identified (94% grade 2, 6.0% grade 3). 106 patients (98%) had upfront surgical resection (60% gross-total resection) with 18% receiving adjuvant radiotherapy (RT). Median time to first progression was 2.5 years (IQR 1.34-4.30). At first recurrence, patients were treated with single or fractionated SRS to a median marginal dose of 16 Gy to a maximum of two lesions (87% received single fraction SRS). Median follow-up time after SRS was 2.6 years. 1-, 2-, and 3-year PFS was 90%, 75%, and 57%, respectively after treatment with SRS. 1-, 2-, and 3-year OS was 97%, 94%, and 92%, respectively. On multivariable analysis, grade 3 disease (HR 6.80; 95% CI 1.61-28.6), male sex (HR 3.48; 95% CI 1.47-8.26), and receipt of prior RT (HR 2.69; 95% CI 1.23-5.86) were associated with worse PFS. SRS dose and tumor volume were not correlated with progression. Treatment was well-tolerated, with a 3.0% incidence of grade 2+ radiation necrosis. This is the largest multi-center study to evaluate salvage SRS in recurrent grade 2 and 3 meningiomas. In this select cohort of patients with primarily grade 2 meningioma with potentially more favorable natural history of delayed, localized first recurrence amenable to salvage SRS, local control rates and toxicity profiles were favorable, warranting further prospective validation