Peñas-Prado, Marta

Abstract INTRODUCTION Prospective studies for adult medulloblastoma (MB) are scarce and management guidelines are largely derived from pediatric experience and retrospective data. However, adult MB is a distinct disease for which limited data exist regarding clinical characteristic, prognostic factors, outcome based on upfront treatment, or patterns of recurrence. METHODS 200 patients (≥18 years at diagnosis) were identified from 1978 to 2017. Survival analysis was performed using the Kaplan-Meier method. RESULTS Median age at diagnosis 29 (18–63); 111 (55.5%) standard-risk (SR), 59 (29.5%) high-risk (HR), 30 (15%) unknown. 188 (94%) and 97 (48.5%) underwent radiotherapy and upfront chemotherapy, respectively. Median PFS: 6.28 years (4.9–11.2); median OS: 8.8 (7.8–12.4) years. Median time to first recurrence: 8.2 (5.1-not reached); 5-year recurrence-free rate: 71% in SR and 45% in HR patients. Survival after first recurrence: 2 years (1.64–2.4). Documented recurrence and risk group were associated with survival (HR 30.4, p< 0.0001 and 2.33, p< 0.001), but metastatic status and local vs. distant recurrence were not. The effect of upfront chemotherapy on survival did not reach statistical significance in SR patients. The use of chemotherapy regimens with or without vincristine or containing cisplatin vs. carboplatin, did not alter the survival outcome. In a subgroup of 57 SR patients who were seen at initial diagnosis and for whom complete staging and treatment information were available 3 and 5-year PFS were 94% (88%, 100%) and 76% (66%, 86%); OS at 5 years, 94% (87%, 100%). CONCLUSION No statistically significant difference was noted in outcome of patients treated without vincristine or with carboplatin instead of cisplatin, suggesting attenuated upfront regimens could be considered to reduce toxicity. Adult MB patients recur late and have a poor post-recurrence survival, therefore long-term follow-up, development of molecular risk-adjusted upfront treatment, and optimization of rescue treatments are needed.

Abstract BACKGROUND A major impediment to improving neuro-oncology outcomes is poor clinical trial accrual. METHODS We convened a multi-stakeholder group including Society for Neuro-Oncology, Response Assessment in Neuro-Oncology, patient advocacy groups, clinical trial cooperative groups, and other partners to determine how we can improve trial accrual. RESULTS We described selected factors contributing to poor trial accrual and possible solutions. We focused on patient and community factors, disparities, physician and provider factors, clinical trial factors, and site and organizational factors CONCLUSIONS We will implement strategies with the intent to double accrual to neuro-oncology trials over the next 5 years.

Background Pituitary carcinoma (PC) is an aggressive neuroendocrine tumor diagnosed when a pituitary adenoma (PA) becomes metastatic. PCs are typically resistant to therapy and develop multiple recurrences despite surgery, radiotherapy and chemotherapy. Recently, treatment with temozolomide (TMZ) has shown promising results, although the lack of prospective trials limits assessment of benefit. Methods We describe a single-center multidisciplinary experience in managing PC patients over a 22-year period and review previously published PC series. Results Seventeen patients were identified. Median age at PC diagnosis was 44 years (range 16–82 years), and the median time from PA to PC transformation was 5 years (range 1–29 years). Median follow-up time was 28 months. Most PCs were hormone-positive (n = 12): ACTH (n = 5), PRL (n = 4), LH/FSH (n = 2) and GH (n = 1). All patients underwent at least one resection and at least one course of radiation after PC diagnosis. Immunohistochemistry showed high Ki-67 labeling index (>3%) in 10/15 cases. Eight patients (47%) had only central nervous system (CNS) metastases; six (35%) had combined CNS and systemic metastases. The most commonly used chemotherapy was TMZ, and TMZ-based therapy was associated with the longest PFS in 12 (71%) cases, as well as the longest period from PC diagnosis to first progression (median 30 months). The 2, 3 and 5-year survival rate of the entire cohort was 71, 59 and 35%, respectively. All patients surviving >5 years had been treated with TMZ-based therapy. Conclusions PC management benefits from multidisciplinary care and multimodality therapy. TMZ-based regimens were associated with high survival rates and long disease control.

Abstract Many factors contribute to the poor survival of malignant brain tumor patients, some of which are not easily remedied. However, one contributor to the lack of progress that may be modifiable is poor clinical trial accrual. Surveys of brain tumor patients and neuro-oncology providers suggest that clinicians do a poor job of discussing clinical trials with patients and referring patients for clinical trials. Yet, data from the Cancer Action Network of the American Cancer Society suggest that most eligible oncology patients asked to enroll on a clinical trial will agree to do so. To this end, the Society for Neuro-Oncology (SNO) in collaboration with the Response Assessment in Neuro-Oncology (RANO) Working Group, patient advocacy groups, clinical trial cooperative groups, including the Adult Brain Tumor Consortium (ABTC), and other partners are working together with the intent to double clinical trial accrual over the next 5 years. Here we describe the factors contributing to poor clinical trial accrual in neuro-oncology and offer possible solutions.

2024 Background: A major impediment to improving neuro-oncology outcomes is poor clinical trial accrual. Methods: We convened a multi-stakeholder group including Society for Neuro-Oncology, Response Assessment in Neuro-Oncology, patient advocacy groups, clinical trial cooperative groups, and other partners to determine how we can improve trial accrual. Results: We describe selected factors contributing to poor trial accrual and possible solutions. Conclusions: We will implement strategies with the intent to double trial accrual over the next 5 years. [Table: see text]

2068 Background: Pituitary carcinoma (PC) is a rare and aggressive neuroendocrine tumor diagnosed once a pituitary adenoma (PA) becomes metastatic. Although no standard treatment currently exists, surgery, radiation (XRT) and/or chemotherapy are most commonly used. Recently, treatment with temozolomide (TMZ) has shown promising results, although the lack of prospective trials limits accurate outcome assessment. Methods: We describe a single-center multidisciplinary team experience in managing PC patients over a 13-year period (Oct, 2003 to Jan, 2017). Results: A total of 17 patients (9 males) were seen. Median age at diagnosis of PC was 44 years (range 16-82 years) and the median time from PA to PC conversion was 6 years (range 1-29 years). Median follow-up time: 28 months (range 8-158 months) with 7 reported deaths. The majority of PC was hormone-secreting (HS) subtype (n = 12): ACTH (n = 5), PRL (n = 4), FSH/LH (n = 2), GH (n = 1). After PC diagnosis, all pituitary tumors were locally invasive, all underwent at least one resection (mean 2.3) and all received at least one course of XRT alone (IMRT = 76%, SRS = 29%, IMPT = 12%) or concurrent with chemotherapy (18%). Immunohistochemistry showed high Ki-67 labeling index ( > 3%) in 9 (53%) cases. Most cases (n = 14) had metastases to the CNS, 35% of those had combined CNS and systemic foci. Ten (59%) cases underwent focal treatment of metastases, 90% of which underwent XRT. The most common chemotherapy used was TMZ [n = 14 (82%): single agent (n = 10); TMZ+capecitabine (n = 5); concurrent TMZ+XRT (n = 3); concurrent TMZ+XRT with adjuvant TMZ (n = 1)]. The median longest progression-free survival (LPFS) was 18 months (range 4-45 months). TMZ was associated with the chemotherapy-related LPFS in 9 (75%) cases. The 2, 3 and 5 year survival rate was 65%, 53% and 35%, respectively. All patients surviving > 5 years were treated with TMZ (n = 5, 2 survived > 10 years). Two refractory cases are currently on PD-1 inhibitor agent. Eighty percent of non-functioning PC were alive at last follow-up (HS-PC, 58%). Recurrence occurred in 11 (65%) cases. Conclusions: Treatment of PC requires a multidisciplinary approach. Multimodality therapy with surgery, radiation and TMZ was associated with higher survival rates and longer PFS.