scholarly journals Isolated Leptomeningeal Progression in a Patient with NTRK Fusion+ Uterine Sarcoma: A Case Report

2021 ◽  
pp. 1841-1846
Author(s):  
Tyler Lanman ◽  
Melanie Hayden Gephart ◽  
Nam Bui ◽  
Angus Toland ◽  
Seema Nagpal
Keyword(s):  
Lung Metastases ◽  
Systemic Disease ◽  
Whole Brain Radiotherapy ◽  
Brain Biopsy ◽  
Complete Response ◽  
Altered Mental Status ◽  
Uterine Sarcoma ◽  
Brain Radiotherapy ◽  
Cns Penetration ◽  
Inhibitor Resistance

While neurotrophic tropomyosin receptor kinase (NTRK) fusions represent rare oncogenic drivers (&#x3c;1% of solid cancers), the recent approval of NTRK inhibitors (larotrectinib and entrectinib) led to dramatic responses in patients with NTRK fusion+ tumors. Both drugs have phase I data, demonstrating efficacy in the central nervous system (CNS), including both primary brain tumors and brain metastases. We present a 29-year-old woman who was diagnosed with <i>NTRK3-SPECC1L</i> fusion+ undifferentiated uterine sarcoma and underwent resection, chemotherapy, and radiotherapy. Two years later, lung metastases were discovered. She was started on larotrectinib with complete response. She remained stable on larotrectinib until she presented with altered mental status and seizures. MRI demonstrated leptomeningeal enhancement, but because leptomeningeal progression from sarcoma is exceedingly rare and her symptoms improved dramatically with antiepileptics, these findings were initially attributed to seizures. After 2 unrevealing lumbar punctures and stable systemic imaging, a brain biopsy demonstrated metastatic sarcoma, still showing NTRK positivity. She underwent whole brain radiotherapy and was switched to entrectinib, but had clinical progression 1 month later and transitioned to hospice. This case demonstrates the efficacy of NTRK inhibitors in rare and aggressive cancer but highlights that these patients can develop isolated CNS progression even in the setting of CNS-penetrant drugs. CNS progression can occur if there is incomplete CNS drug penetration, discordance in molecular profiles between CNS and systemic disease, or acquired NTRK inhibitor resistance. In this case, CNS disease maintained the NTRK fusion status, but either inadequate CNS penetration or development of a resistance gene may explain the isolated CNS progression.

scholarly journals RTHP-34. IMPROVED SURVIVAL IN CNS LYMPHOMA WITH SALVAGE LOW-DOSE WHOLE-BRAIN RADIOTHERAPY WITH FOCAL BOOST AND CONCURRENT TEMOZOLOMIDE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi217-vi217
Author(s):  
Katherine Selwa ◽  
Anna Laucis ◽  
Theodore Lawrence ◽  
Larry Junck ◽  
Kyle Cuneo ◽  
...  
Keyword(s):  
Low Dose ◽  
Radiation Treatment ◽  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Complete Response ◽  
Concurrent Chemotherapy ◽  
Cns Lymphoma ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Kaplan Meier

Abstract OBJECTIVE There is no standard salvage radiotherapy (RT) regimen, nor a consensus on the concurrent chemotherapy use in CNS lymphoma. We assessed the efficacy of low-dose whole-brain radiotherapy (WBRT) with focal-boost to the area of disease and concurrent temozolomide for the salvage treatment of CNS lymphoma. METHODS A single center retrospective study of CNS lymphoma patients seen between 01/2004 and 02/2019. The inclusion criteria were: diagnosis of CNS lymphoma, age > 18 years at diagnosis, radiation treatment to the brain, and formulation of plan at University of Michigan with at least one follow-up. Overall survival (OS) was determined by Kaplan Meier method. RESULTS Out of 93 patients (median age 58, 45% female), 73% were diagnosed with primary CNS lymphoma (n=68), and the remainder with secondary CNS lymphoma. Radiation modalities were WBRT alone (n=52), low-dose WBRT + focal boost (n=33) and focal RT alone (n=8). Twenty-six patients (28%) received concurrent temozolomide with radiation. Those who received WBRT+boost achieved complete response at a significantly higher rate than those who received WBRT alone (36% vs 17% respectively, p=0.047). The median OS among all groups was 45 months. There was a significant improvement in OS in patients receiving low-dose WBRT+boost compared to WBRT alone (median 65 vs 14 months respectively, p=0.016). OS was significantly longer in patients who received concurrent temozolomide than in those who did not (median 86 vs 23 months respectively, p=0.0287). CONCLUSIONS In CNS lymphoma salvage RT, a longer survival was observed with low-dose WBRT with focal-boost compared to WBRT alone, as well as with concurrent temozolomide. This result is limited by the selection bias to each of the treatment groups; however, the low-dose WBRT with focal-boost and concurrent temozolomide is a useful salvage alternative to standard WBRT as it may reduce long-term neurocognitive toxicity.

Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery (SRS) in patients with 1-3 newly diagnosed brain metastases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2018-2018
Author(s):  
David M. Peereboom ◽  
Samuel T. Chao ◽  
John H. Suh ◽  
Ding Wang ◽  
Tom Mikkelsen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Brain Metastases ◽  
Systemic Disease ◽  
Neuropsychological Testing ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Growth Factor Signaling ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Primary Disease

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).

scholarly journals Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: CALGB 50202 (Alliance 50202)

2013 ◽  
Vol 31 (25) ◽  
pp. 3061-3068 ◽  
Author(s):  
James L. Rubenstein ◽  
Eric D. Hsi ◽  
Jeffrey L. Johnson ◽  
Sin-Ho Jung ◽  
Megan O. Nakashima ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Remission Induction ◽  
Cns Lymphoma ◽  
High Dose ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Myeloablative Chemotherapy

Purpose Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma (PCNSL). We performed a multicenter study of high-dose consolidation, without WBRT, in PCNSL. Objectives were to determine: one, rate of complete response (CR) after remission induction therapy with methotrexate, temozolomide, and rituximab (MT-R); two, feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine (EA); three, progression-free survival (PFS); and four, correlation between clinical and molecular prognostic factors and outcome. Patients and Methods Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R, and patients who achieved CR received EA consolidation. We performed a prospective analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial. Results The rate of CR to MT-R was 66%. The overall 2-year PFS was 0.57, with median follow-up of 4.9 years. The 2-year time to progression was 0.59, and for patients who completed consolidation, it was 0.77. Patients age > 60 years did as well as younger patients, and the most significant clinical prognostic variable was treatment delay. High BCL6 expression correlated with shorter survival. Conclusion CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT.

Clinical evidence for drug penetration of capecitabine and lapatinib uptake in resected brain metastases from women with metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 514-514 ◽  
Author(s):  
Aki Morikawa ◽  
David M. Peereboom ◽  
Quentin R Smith ◽  
Helen Thorsheim ◽  
Paul R Lockman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Whole Brain Radiotherapy ◽  
Clinical Activity ◽  
Brain Radiotherapy ◽  
Her2 Breast Cancer ◽  
Drug Concentrations ◽  
Cns Penetration ◽  
Preclinical Animal Models

514 Background: Brain metastasis (BM) is a challenging complication of metastatic breast cancer (MBC). Although systemic therapy is not commonly considered as a primary therapeutic approach, its potential in BM management has recently become apparent (Bachelot T et al Lancet Oncol 2013). Capecitabine and lapatinib in particular have been evaluated in HER2+ breast cancer BM (BCBM), but evidence for drug/metabolite CNS penetration is solely derived from preclinical animal models. In this study, we examined capecitabine, its metabolites, and lapatinib uptake in BCBMs resected due to medically indicated craniotomy. Methods: Study patients had BCBM requiring surgical resection. Patients with HER2-negative MBC received a single preoperative oral dose of capecitabine (1250mg/m2) 2-3 hrs before surgery. Those with HER2+ MBC received 2-3 oral doses of lapatinib (1250mg) daily, the last dose 2-3 hrs before surgery. On the day of surgery, serum was collected serially starting just before drug administration, intraoperatively, and through one hour after the conclusion of surgery. The concentration of capecitabine, its metabolites, and lapatinib from serum and BM were measured using liquid chromatography with tandem mass spectroscopy (LC-MS/MS). Results: 10 patients enrolled; PK data is available for 9: 6 for capecitabine and 3 for lapatinib. Capecitabine, its intermediate metabolites, 5FU, and lapatinib were detected in all BMs. Tumor capecitabine and 5-FU concentrations ranged from 3% to 129% and from 168% to 1422%, respectively, of serum concentrations. For lapatinib, the range was 21% to 700%. In a number of the BMs, drug concentrations were in the therapeutic range, whereas in others the concentrations were up to 10 fold lower. Conclusions: This is the first study to show capecitabine and lapatinib were detected in clinically relevant concentrations in a number of non-irradiated human BCBMs. This provides evidence for their ability to cross the blood-brain barrier, is consistent with prior published clinical activity, and supports further evaluation in a clinical setting prior to whole brain radiotherapy. Clinical trial information: NCT00795678.

scholarly journals Gestational Choriocarcinoma Presenting with Lacrimal Gland Metastasis: A First Reported Case

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Naushad A. B. Ahamed ◽  
Khalid Sait ◽  
Nisreen Anfnan ◽  
Khader Farwan ◽  
S. H. M. Nizamuddin ◽  
...  
Keyword(s):  
Lacrimal Gland ◽  
Hydatidiform Mole ◽  
Whole Brain Radiotherapy ◽  
Complete Response ◽  
Orbital Metastasis ◽  
Gestational Choriocarcinoma ◽  
Brain Radiotherapy ◽  
Normal Limits ◽  
First Case ◽  
Methotrexate Chemotherapy

Background. Gestational choriocarcinoma (GC) is a recognized clinicopathological subtype of gestational trophoblastic neoplasia that usually metastasizes hematogenously to highly vascular organs like the lung, liver, and brain. However, orbital metastasis to the choroid and lacrimal gland is a rare occurrence.Case Presentation. A 21-year-old female presented with headache and left orbital swelling one year after resection of a complete hydatidiform mole followed by adjuvant methotrexate chemotherapy. A metastatic imaging screening revealed multiple metastases in the lungs, brain, and adrenal gland, in addition to the choroid and lacrimal gland. Based on her modified WHO risk factors scoring she was started on chemotherapy and whole brain radiotherapy, which resulted in a complete response. At two-year follow-up, serum b-HCG level was with normal limits; imaging surveillance was uneventful.Conclusion. We present the first case of lacrimal gland metastasis in a young girl from GC relapse.

scholarly journals Survival in Melanoma Brain Metastases in the era of novel systemic therapies

2020 ◽  
Author(s):  
Joseph P Merola ◽  
Joanita Ocen ◽  
Satish Kumar ◽  
James Powell ◽  
Caroline Hayhurst
Keyword(s):  
Brain Metastases ◽  
Demographic Data ◽  
Systemic Disease ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Poor Overall Survival ◽  
Aggressive Approach ◽  
Brain Radiotherapy ◽  
Melanoma Brain Metastases ◽  
Receive Treatment

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.

Treatment of small cell lung cancer with VP-16, vincristine, doxorubicin (Adriamycin), cyclophosphamide (EVAC), and high-dose chest radiotherapy.

1983 ◽  
Vol 1 (8) ◽  
pp. 483-488 ◽  
Author(s):  
G E Goodman ◽  
T P Miller ◽  
M M Manning ◽  
S L Davis ◽  
L J McMahon
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Whole Brain Radiotherapy ◽  
Complete Response ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Brain Radiotherapy

Seventy-one previously untreated patients with small cell lung cancer (SCLC) received a combination of VP-16, vincristine, doxorubicin (Adriamycin), and cyclophosphamide (EVAC) repeated every three weeks. Limited-disease (LD) patients and extensive-disease (ED) patients achieving a complete response (CR) or partial response (PR) after four to six cycles of EVAC received 4,000 rads over four weeks whole-brain radiotherapy (RT) and 5,000 rads over five weeks RT to the original pulmonary primary and mediastinum. ED patients with persisting disease outside the chest after six cycles of EVAC continued chemotherapy and did not receive RT. After RT was completed, EVAC was continued for a total treatment duration of 24 months. Of 65 patients evaluable for response 76% (25 of 33) of LD patients and 34% (11 of 32) of ED patients achieved a CR prior to RT; two additional ED patients achieved a CR after RT. Median survival for all 71 patients was 48 weeks (range, one to 207 weeks); median survival for 33 LD patients was 92 weeks and for 38 ED patients it was 36 weeks. Nine of 25 LD patients and 10 of 13 ED patients have relapsed from CR. The EVAC-RT protocol is promising in view of the high CR rate and long remission duration achieved, especially among patients with LD.

scholarly journals ML-07 R-MPV-A THERAPY FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN THE ELDERLY: OUTCOME AND PROBLEM

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii33-ii33
Author(s):  
Hirotaka Fudaba ◽  
Yasutomo Momii ◽  
Kouhei Onishi ◽  
Daigo Asou ◽  
Minoru Fujiki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Partial Response ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Complete Response ◽  
The Other ◽  
Brain Radiotherapy ◽  
Group A ◽  
Group B

Abstract PURPOSE R-MPV-A therapy has recently been reported to improve the outcomes of primary central nervous system lymphoma (PCNSL). Our patients have received R-MPV-A therapy since 2017 and elderly patients have only been treated with whole brain radiotherapy when they do not show a complete response after induction chemotherapy. We report the therapeutic outcomes and problems of elderly PCNSL patients treated with R-PMV-A. MATERIALS & METHODS Eight newly diagnosed PCNSL patients received R-MPV therapy from September 2017 to June 2019. We retrospectively reviewed the cycles of R-MPV therapy, radiotherapy, consolidation high-dose Ara-C (HD-Ara-C) therapy, and the G8 score (a geriatric assessment). RESULTS Patients were divided into three groups: Group A (71–75 years; n=2), Group B (76–80 years; n=4), and Group C (&gt;81 years; n=2). All Group A patients finished 5 cycles of R-MPV therapy, showed a complete response, and underwent consolidation HD-Ara-C therapy. Two Group B patients showed a complete response on R-MPV therapy. One of the other patients showed a partial response after 3 cycles of R-MPV therapy, and a &gt;3 kg reduction in body weight. The patient’s G8 score was 12 points. Whole brain radiotherapy (23.4 Gy) was administered followed by local radiotherapy (21.6 Gy). One patient showed a partial response after 7 cycles of R-MPV therapy and started radiotherapy. One Group C patient received radiotherapy after 3 cycles of R-MPV because of a new lesion. The other Group C patient showed acute renal damage after 3 cycles of R-MPV. CONCLUSION R-MPV-A therapy was relatively safe for our elderly PCNSL patients. Notably, patients &gt;76 years of age sometimes had severe adverse effect with increased R-MPV cycles. A promising therapeutic strategy based on age and geriatric assessment is needed.

The treatment of recurrent brain metastases with stereotactic radiosurgery.

1990 ◽  
Vol 8 (4) ◽  
pp. 576-582 ◽  
Author(s):  
J S Loeffler ◽  
H M Kooy ◽  
P Y Wen ◽  
H A Fine ◽  
C W Cheng ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Linear Accelerator ◽  
Systemic Disease ◽  
Performance Status ◽  
Whole Brain Radiotherapy ◽  
Metastatic Lesion ◽  
Slight Reduction ◽  
Brain Radiotherapy ◽  
Solitary Metastases

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.

scholarly journals The Expanding Role of Radiosurgery for Brain Metastases

2018 ◽  
Author(s):  
Mark O'Beirn ◽  
Helen Benghiat ◽  
Sara Meade ◽  
Geoff Heyes ◽  
Vijay Sawlani ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Local Control ◽  
Systemic Disease ◽  
Whole Brain Radiotherapy ◽  
Targeted Agents ◽  
Brain Radiotherapy ◽  
Multiple Metastases ◽  
Rising Incidence ◽  
Molecular Information

Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole brain radiotherapy (WBRT) improved local control rates versus WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.

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