scholarly journals THER-02. PARP Inhibitor Tolerability and Impact on Progression-Free Survival in Patients with High-Grade, Ovarian Carcinoma with Brain Metastasis: A Case-Series

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii12-iii13
Author(s):  
Alexander Mohler ◽  
Belkys Salinas ◽  
Karissa Nazur ◽  
Yazmin Odia ◽  
Nicholas Lambrou

Abstract Brain metastases secondary to ovarian carcinoma is an uncommon but increasing phenomenon. PARP inhibitors (PARPi) are increasingly used as an adjunctive treatment in patients with central nervous system metastases (CNS). Historically brain metastases has a historically poor prognosis. Five women with a mean age of 60.4 ± 7.6 years were included. All had stage IIIC/IV ovarian cancer and diagnosed with brain metastases at recurrence. Three underwent resection for oligometastatic disease followed by post-operative stereotactic radiosurgery (SRS), one had SRS without surgery, and one patient underwent whole brain radiotherapy for multiple metastases. Pathology was confirmed in those who were resected. Two patients had evidence of systemic disease in addition to CNS spread. Three women were BRCA1/2 Positive. Following initial radiotherapy, one patient received adjuvant chemotherapy followed by olaparib maintenance, one received 13 cycles of bevacizumab/olaparib, followed by olaparib maintenance. A third patient was treated with olaparib/bevacizumab and two patients received olaparib monotherapy, both of whom continued on therapy. All received olaparib therapy during their treatment and all had minor dose modifications due to side effects. Mean survival from initial cancer diagnosis was 62.4 ± 20.4 months. Mean duration of PARPi therapy was 27.6 ± 16.8 months. Mean survival following CNS recurrence was 22.8 ± 12 months. One patient is disease-free, two patients are alive with stable disease, one patient is alive but off treatment secondary to progression, and one patient is deceased secondary to progression of her brain metastases after being on PARP therapy for 18 months. The cohort remained highly functional across the trajectory of their disease with ECOG scores of 1 (n=4) or 0 (n=1). The results of this single institution retrospective evaluation suggest olaparib in combination with radiotherapy +/- bevacizumab is well tolerated and can provide additional benefit in patients with brain metastases secondary to ovarian carcinoma.

Author(s):  
Joseph P Merola ◽  
Joanita Ocen ◽  
Satish Kumar ◽  
James Powell ◽  
Caroline Hayhurst

Abstract Background Melanoma brain metastases (MBM) have historically poor overall survival (OS). Recently introduced systemic anticancer therapies (SACT), namely targeted therapies (TT) such as BRAF inhibitors and immunotherapy (IO), to control advanced disease have shown improved survival. Today, increasingly aggressive strategies are sought for MBM. We review outcomes in MBM after surgery or stereotactic radiosurgery (SRS) and the survival impact in advanced systemic disease when combined with novel anticancer therapies. Methods Retrospective cohort study of patients referred to a regional neuro-oncology multidisciplinary (MDT) meeting with MBM. Demographic data, extent of systemic disease and data on surgical and oncological management were collected, plus use of SACT. The primary outcomes were median OS, 12 and 24 month survival and progression-free survival. Results Between 2010 – 2018 142 patients with MBM were referred. Following the introduction of SACT the rate of referrals to MDT more than doubled from 11.6 to 25.7 patients per year. A focal brain metastasis was treated surgically in 23 (16.2%) patients, and by SRS in 29 (20.4%). 56 (39.4%) patients underwent palliative whole brain radiotherapy (WBRT) and 34 (23.9%) did not receive treatment. Median OS was 11 months for the surgical cohort, 9 months for the SRS cohort and increased when treatment with or without SACT was considered to 23 months and 12 months respectively. Conclusion In the setting of SACTs, survival in MBM is significantly improved after surgery or SRS even in patients with advanced and uncontrolled systemic disease at the time of presentation, supporting an aggressive approach to MBM management.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19063-e19063
Author(s):  
K. Kim ◽  
J. Lee ◽  
M. Chang ◽  
J. Uhm ◽  
J. A. Yun ◽  
...  

e19063 Background: Approximately 25 to 30% of patients with lung cancer develop brain metastases at some stage and 12∼18% at the time of initial presentation. Whole brain radiotherapy (WBRT) has long been a mainstay of treatment of brain metastases. Another treatment approach, Stereotactic radiosurgery (SRS) is a method of delivering high doses of focal irradiation to a tumor while minimizing the irradiation to the adjacent normal tissue. However, the prognosis of NSCLC patients with asymptomatic brain metastases, who are not treated with SRS or WBRT, has not been fully investigated yet. This study aimed to analyze the outcome for various treatment modalities in NSCLC patients with asymptomatic brain metastases. Methods: We reviewed the medical records of 129 patients with a histopathologically proven NSCLC and a synchronous brain metastases between January 2003 and December 2007. The patients were categorized as primary chemotherapy, primary SRS, and primary WBRT group: primary chemotherapy (78 patients), primary SRS (24 patients), and primary WBRT (27 patients). Results: With median follow-up of 30.0 months (7.2 -70.7), the median overall survival (OS) for the entire patients was 15.6 months (0.5–50.7) and the progression free survival (PFS) was 6.1 months (0.3- 53.0). The OS was 22.4m for primary SRS group, 13.9m for primary chemotherapy group, and 17.7m for primary WBRT group; p=0.86). However, patients treated with primary SRS showed trend toward prolonged survival compared to those of primary WBRT p=0.06). Subset analysis of 110 adenocarcinoma patients showed that the median OS for patients treated with primary SRS was longer than those of primary WRBT (29.3m vs 17.7m p=0.01) or primary chemotherapy (29.3m vs 14.6m p=0.04). Conclusions: These results suggest that for NSCLC patients with asymptomatic brain metastases at first diagnosis, SRS rather than primary chemotherapy or WBRT might be considered as initial treatment, especially for patients with adenocarcinoma. No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13589-e13589
Author(s):  
Alicia Marin ◽  
Margarita Martin ◽  
Emma Gonzalez ◽  
Lisselott Torres ◽  
David Hernandez ◽  
...  

e13589 Background: We report our experience with volumetric modulated arc therapy (VMAT-IGRT) use to plan and deliver whole brain radiotherapy whit a simultaneous integrated boost in patients with brain metastases, using hippocampal sparing. Methods: In this retrospective study 57 patients with brain metastases were treated with radiotherapy VMAT-IGRT were administered in 12 daily fractions of 2.7Gy for a total of 32.4Gy (EBD 40Gy) to whole-brain and simultaneous integrated boost to brain metastases, multiple targets, in 12 fractions to 3.4Gy for a total dose of 40.8Gy (EBD 60Gy). The primary endpoint was intracranial progression-free survival (PFS) and secondary endpoints were preserves neurocognitive function and overall survival (OS). Survival rates were determined by Kaplan-Meier method. Differences between survival curves were analyzed by the log-rank test. Results: From January 2015 to December 2018, 57 patients were enrolled. The median follow-up time was 7 months. PFS6, PFS12 and PFS18 were 91.3%, 70.8% and 70.8% respectively. mOS, OS6, OS12 and OS18 were 10 months (95% IC 4.2-15.7 months), 67.2%, 48.6% and 35.3% respectively. Response rates were as follows: 29RC (50.9%), 21RP (36.8%), 7SD (12.3%) and 0PD (0%). Long progression-free survival patients: PFS > 12, 15 and 18 months for initial diagnosis 70%, 70% and 70% respectively. Conclusions: Whole-brain radiotherapy with simultaneous integrated boost to brain-metastases: VMAT-IGRT is safe and promising and possibly produces survival and tolerance benefits. Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2018-2018
Author(s):  
David M. Peereboom ◽  
Samuel T. Chao ◽  
John H. Suh ◽  
Ding Wang ◽  
Tom Mikkelsen ◽  
...  

2018 Background: For patients with 1-3 brain metastases, standard therapy after SRS is adjuvant whole brain radiotherapy (WBRT). SRS without WBRT carries a higher rate of brain relapse. Due to concerns about neurologic sequelae of WBRT, however, many patients and physicians opt to defer WBRT until the time of central nervous system (CNS) progression. This trial used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy. Sunitinib inhibits vascular endothelial growth factor signaling, and we hypothesized that it would prevent growth of microscopic brain metastases presumed to be present. The objective was to use adjuvant sunitinib after SRS to prevent the emergence of new or progressive disease in the brain or at the site of SRS and to preserve neurocognitive function. Methods: Eligible patients had 1-3 newly diagnosed brain metastases, RTOG RPA class 1-2, and started sunitinib < 1 month after SRS and baseline neuropsychological testing (NPT). Patients with controlled systemic disease were allowed to continue chemotherapy for their primary disease according to a list of published regimens (therapy + sunitinib) included in the protocol. Patients received sunitinib 37.5 or 50 mg/d days 1-28 every 42 days until CNS progression. NPT and MRIs were obtained every 2 cycles. The primary endpoint was the rate of CNS progression at 6 months (PFS6) after SRS. Results: Fourteen patients enrolled. The median age was 59 (range 46-80). Main histologies: lung 36%, breast 21%, melanoma 14%. Toxicities: Grade 4: neutropenia [ANC] (1 pt); Grade 3: fatigue (5), ANC (2), rash (1). Dose reduction due to toxicity: 1 pt (to 37.5 mg/d). The CNS PFS6 and PFS12 were 50% + 13% and 43% + 13%, respectively. The median PFS was 6.6 months (95% C.I. 1.5-19). NPT results will be reported at the meeting. Conclusions: Sunitinib after SRS for 1-3 brain metastases was well tolerated with a PFS6 of 50%. The use of novel agents to prevent progressive brain metastasis after SRS requires the incorporation of chemotherapy regimens to control the patient’s primary disease. Future trials should continue to explore the paradigm of secondary chemoprevention of brain metastases after definitive local therapy (surgery or SRS).


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2016-2016
Author(s):  
Yu Yang Soon ◽  
Ivan Weng Keong Tham ◽  
Keith Hsiu Chin Lim ◽  
Wee Yao Koh ◽  
Jiade Jay Lu

2016 Background: The benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to determine the efficacy and safety of additional upfront WBRT. Methods: We searched MEDLINE, EMBASE, CENTRAL from date of inception and annual meeting proceedings of ASCO and ASTRO from 1999 to September 2011 for RCTs comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), quality of life (Qol) and neurological toxicity. Hazard ratios (HR), confidence intervals (CI), p values (p) were estimated with random effects models using Revman 5.1. Results: We found five RCTs including 663 patients with one to four brain metastases. Adding upfront WBRT decreased the one-year incidence of any intracranial disease progression from 73-76% to 22 - 47% but did not improve OS (HR 1.11, 95%CI 0.83 - 1.48, p = 0.47) and PFS (HR 0.76, 95%CI 0.53 - 1.10, p = 0.14). Subgroup analyses showed that the effects on overall survival are similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The effects of upfront WBRT on NF, Qol and neurological toxicity were variable. Conclusions: Adding upfront WBRT to surgery or SRS significantly decreased any intracranial disease progression at one year but did not improve overall and progression free survival and produced variable effects on neurocognitive function, quality of life and neurological toxicity when compared with surgery or SRS alone. Future research should focus on developing more effective approaches to characterize and ameliorate the potential neurological toxicity of WBRT.


Neurosurgery ◽  
2018 ◽  
Vol 83 (3) ◽  
pp. 566-573 ◽  
Author(s):  
Rami A El Shafie ◽  
Angela Paul ◽  
Denise Bernhardt ◽  
Henrik Hauswald ◽  
Thomas Welzel ◽  
...  

Abstract BACKGROUND Neurosurgical resection is recommended for symptomatic brain metastases, in oligometastatic patients or for histology acquisition. Without adjuvant radiotherapy, roughly two-thirds of the patients relapse at the resection site within 24 mo, while the risk of new metastases in the untreated brain is around 50%. Adjuvant whole-brain radiotherapy (WBRT) can reduce the risk of both scenarios of recurrence significantly, although the associated neurocognitive toxicity is substantial, while stereotactic radiotherapy (SRT) improves local control at comparably low toxicity. OBJECTIVE To compare locoregional control and treatment-associated toxicity for postoperative SRT and WBRT after the resection of 1 brain metastasis in a single-center prospective randomized study. METHODS Fifty patients will be randomized to receive either hypofractionated SRT of the resection cavity and single- or multisession SRT of all unresected brain metastases (up to 10 lesions) or WBRT. Patients will be followed-up regularly and the primary endpoint of neurological progression-free survival will be assessed by magnetic resonance imaging (MRI). Quality of life and neurocognition will be assessed in 3-mo intervals using standardized tests and EORTC questionnaires. EXPECTED OUTCOMES We expect to show that postoperative SRT of the resection cavity and further unresected brain metastases is a valid means of improving locoregional control over observation at less neurocognitive toxicity than caused by WBRT. DISCUSSION The present study is the first to compare locoregional control as well as neurocognitive toxicity for postoperative SRT and WBRT in patients with up to 10 metastases, while utilizing a highly sensitive and standardized MRI protocol for treatment planning and follow-up.


ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ettie Piura ◽  
Benjamin Piura

This paper will focus on knowledge related to brain metastases from ovarian carcinoma. So far, less than 600 cases were documented in the literature with an incidence among ovarian carcinoma patients ranging from 0.29% to 11.6%. The ovarian carcinoma was usually an advanced-stage epithelial serous carcinoma, and the median interval between diagnosis of ovarian carcinoma and brain metastases was 2 years. Most often, brain metastases, affected the cerebrum, were multiple and part of a disseminated disease. Treatment of brain metastasis has evolved over the years from whole brain radiotherapy (WBRT) only to multimodal therapy including surgical resection or stereotactic radiosurgery followed by WBRT and/or chemotherapy. The median survival after diagnosis of brain metastases was 6 months; nevertheless, a significantly better survival was achieved with multimodal therapy compared to WBRT only. It is suggested that brain imaging studies should be included in the followup of patients after treatment for ovarian carcinoma.


Author(s):  
Fred Hsu ◽  
Alan Nichol ◽  
Roy Ma ◽  
Para Kouhestani ◽  
Brian Toyota ◽  
...  

AbstractBackground: To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. Methods: We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. Results: For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Conclusions: Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8529-8529 ◽  
Author(s):  
Michele Maio ◽  
Alessandro Testori ◽  
Paolo Antonio Ascierto ◽  
Ruggero Ridolfi ◽  
Mario Santinami ◽  
...  

8529 Background: Patients (pts) with metastatic melanoma (MM) often develop treatment-resistant brain metastases (mets). Treatment includes fotemustine (FTM), which crosses the blood-brain barrier. Ipilimumab (ipi) has shown activity in pts with MM and asymptomatic brain mets (Heller et al. ASCO 2011; abs 8581). In the phase II NIBIT-M1 trial, MM pts with asymptomatic brain mets were eligible for treatment with ipi plus FTM. Here, data from this pt subset are reported. Methods: Eligible pts received induction therapy with ipi 10 mg/kg every 3 wks (Q3W) x4 and FTM 100 mg/m2 weekly for 3 wks, followed by ipi Q12W from Week (W) 24 and FTM Q3W from W9. The primary objective was the immune-related (ir) disease control rate (irDCR: complete/partial response [CR/PR] or stable disease [SD] using the ir response criteria). Secondary objectives included ir objective response rate (ORR) and progression-free survival (PFS); overall survival (OS), and safety. Tumor assessments were performed Q8W from W12 to W36 and Q12W thereafter. Results: Among 86 enrolled pts, 20 had brain mets. Of these, 7 had prior whole brain radiotherapy (n=4) or radiosurgery (n=3). As of December 2011, the irDCR was 50% (10/20; 95% CI, 27.2–72.8%) with an irORR of 40% (95% CI, 19.1–63.9%: 2 CRs and 6 PRs). Pts with irDC also had stability/reduction (n=5) or disappearance (n=5) of brain mets. Among pts with progressive disease, all but one had progression in the brain. With median follow-up of 8.3 months (range: 0.4–16.9), median irPFS was 4.6 months (95% CI, 0.7–12.3). The 1-year OS rate was 52.9% (95% CI, 26.6–79.2); median OS was not reached. Induction with ipi and FTM was completed by 55% and 85% pts, respectively. Grade 3/4 drug-related adverse events (AEs) occurred in 60% pts; most commonly myelotoxicity (50%), increased ALT/AST (5%) and gastrointestinal (5%). AEs were generally manageable and reversible per protocol guidance. CNS AEs of any grade (i.e., haemorrhage, headache and seizure) occurred in 25% pts (grade 3/4 in 2 pts) and were attributed to disease progression. Conclusions: The combination of ipi plus FTM is active and safe in pts with MM and brain mets, regardless of prior treatment, and will be further explored in the phase III NIBIT-M2 trial.


1990 ◽  
Vol 8 (4) ◽  
pp. 576-582 ◽  
Author(s):  
J S Loeffler ◽  
H M Kooy ◽  
P Y Wen ◽  
H A Fine ◽  
C W Cheng ◽  
...  

Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of (or stable) systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy.


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