scholarly journals Clinical Analysis of Pediatric Systemic Juvenile Xanthogranulomas: A Retrospective Single-Center Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongyun Lian ◽  
Ang Wei ◽  
Lejian He ◽  
Ying Yang ◽  
Honghao Ma ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Manifestations ◽  
Stable State ◽  
Central Nervous System Involvement ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Chemotherapy ◽  
First Line Treatment

Objective: To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG).Methods: Clinical data of children with JXG who were hospitalized in Beijing Children's Hospital, Capital Medical University, from January 2012 to December 2019 were retrospectively analyzed, including clinical manifestations, laboratory determinations, treatment, and prognosis of the children. Patients were treated with vindesine + prednisone as the first-line treatment and cytarabine + vindesine + dexamethasone ± cladribine as the second-line treatment.Results: Ten patients, including 8 males and 2 females, with a median of onset age of 1.95 (0.80–7.30) years, exhibited multi-system dysfunction. The median age of diagnosis was 2.45 (1.30–12.10) years. The most common location of extracutaneous lesions was the central nervous system (6 cases), followed by the lung (5 cases) and bone (4 cases). Nine patients underwent first-line chemotherapy, and 6 patients underwent second-line chemotherapy, including 5 patients with poorly controlled disease after first-line treatment. The median observation time was 29 (3–115) months. Nine patients survived, whereas one patient died of respiratory failure caused by pulmonary infection. At the end of follow-up, 7 patients were in active disease (AD)/regression state (AD-better), and 2 patients were in an AD/stable state (AD-stable). Three patients had permanent sequelae, mainly central diabetes insipidus. The rates of response to the first-line treatment and the second-line treatment were 40.0 and 66.7% respectively.Conclusion: The chemotherapy protocol for Langerhans cell histiocytosis (LCH) may be effective for patients with systemic JXG. Central nervous system involvement may not impact overall survival, but serious permanent sequelae may occur.

High Efficiency of ICE (Ifosfamide-Carboplatin-Etoposide) in Relapse/Refractory Primary Central-Nervous System and Intra-Ocular Non Hodgkin Lymphoma, After First Line Treatment Containing High Doses of Methotrexate and Cytarabine. A Monocentric Retrospective Study From 2010 to 2012 On 17 Cases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3664-3664 ◽  
Author(s):  
Sylvain Choquet ◽  
Damien roos Weil ◽  
Khe Hoang Xuan ◽  
Nathalie Cassoux ◽  
Helene Merle-Beral ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hodgkin Lymphoma ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Line Treatment ◽  
First Line ◽  
Non Hodgkin Lymphoma ◽  
High Doses ◽  
First Line Treatment

Abstract Abstract 3664 Background: Primary central nervous system lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL) are at very high risk of relapse after a first line treatment, and then carry a very poor prognosis. Autologous stem cell transplantation (ASCT) can offer prolonged responses but its results clearly depend on efficiency of salvage chemotherapy (Soussain, haemtologica, 2012). Since recent publications on first line treatment of PCNSL and PIOL recommend high dose methotrexate (Mtx) and cytarabine (AraC) (Ferreri, Lancet 2009), salvage chemotherapy must use other drugs with high level of penetration in the central nervous system (CNS). In this setting, ICE regimen, validated in systemic non Hodgkin lymphoma, seems to be appropriated but no data is published in PCNSL and PIOL. Methods: From june 2010 to may 2012, all relapse/refractory PCNSL and PIOL treated in first line by high doses of Mtx and AraC in the Pitie-Salpetriere Hospital, Paris, France, where treated by ICE regimen : ifosfamide (5g/m2 at day 2), carboplatine (AUC 5 at day 2) and etoposide (100mg/m2/d days 1 to 3). Doses where adapted on patient general status and ASCT proposed when possible. Results: Seventeen patients have been treated, 7 females and 10 males, median age 62 [28–84]. Four where refractory and 13 in relapse, with a mean progression free survival (PFS) of 368 days [85–1763], 4 had a second line, one a third before ICE. At moment of ICE treatment, localizations where 10 CNS, 2 CNS + PIOL, 3 PIOL and 2 meningitis. The mean number of cycles was 4 [1–6] and 4 patients needed a dose reduction. During treatment, grade 3/4 WHO toxicities where: 6 neutropenic fever (one death), 5 anemia, 9 neutropenia, 10 thrombopenia and one CNS complication (coma and hypersalivation). ASCT have been made in 6 patients (5 in CR, 1 in PR) and are pending in 3. Complete response (CR) have been obtained in 13 patients (76%), partial in 2. With a mean follow-up of 405 days, 6/15 patients in response relapsed (only one after ASCT), in a median of 81 days, 9 patients died (7 by progression, one during treatment and one in CR). Median Overall survival (OS) was 220 days for all patients but was not reached in case of ASCT. Conclusion: ICE regimen is very effective in relapse/refractory PCNSL and PIOL heavily treated by high dose Mtx and AraC. This efficacy can allow to perform ASCT in eligible patients, chemosensitivity being the most important factor influencing the OS and PFS after ASCT. ICE can represent a new standard in this setting. Disclosures: Leblond: Roche: Advisory Board Other, Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen-Cilag: Honoraria.

scholarly journals Primary Central Nervous System Lymphoma and the Blood-Brain Barrier

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 928-928
Author(s):  
Nancy D. Doolittle ◽  
Rochelle Fu ◽  
Prakash Ambady ◽  
Edward A Neuwelt
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Disease Control ◽  
Central Nervous System Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Anti Cd20 ◽  
Bbb Opening ◽  
First Line Treatment

Abstract Recent reports propose high-dose (HD) methotrexate (MTX)-based cytoreduction followed by consolidation with HD chemotherapy (HDC) with or without autologous stem-cell transplantation (ASCT) as first-line treatment for primary central nervous system lymphoma (PCNSL). The main rationale is that HDC-ASCT may improve disease control by achieving higher therapeutic concentrations of cytotoxic chemotherapy in the CNS, thus circumventing the blood-brain barrier (BBB). We have employed an alternative approach to treat PCNSL patients effectively. This first-line treatment enhances delivery of standard dose (SD) MTX-based chemotherapy administered intra-arterially (i.a.) with osmotic BBB opening plus the anti-CD20 monoclonal antibody (mAb) rituximab, followed in complete responders by anti-CD20 mAb maintenance immunotherapy. The main features that distinguish our approach from HDC-ASCT consolidation are to utilize BBB properties to maximize delivery of SD chemotherapy to the CNS sanctuary, and maintenance immunotherapy to delay recurrence. A multi-center study of 149 PCNSL patients (2,079 i.a. BBB treatments) resulted in one death within 48 hrs after treatment, from pulmonary embolism. Prior to routine use of granulocyte colony stimulating factor, granulocytopenic fever occurred in 3% of BBB treatments (Angelov, J Clin Oncol 2009). This contrasts with HDC-ASCT consolidation which carries substantial morbidity and treatment-related mortality (6% to 9%) (Ferrari, Lancet Hemat 2016; Omuro, Blood 2015). Further, HDC-ASCT is used primarily in younger PCNSL patients (< 60-65 yrs) with good performance status and is not feasible in many PCNSL patients given the median age at diagnosis is 60-65 yrs. First-line enhanced BBB delivery of SD MTX-based chemotherapy in 149 patients provided an overall response rate (ORR) of 82% (58% CR rate) and median overall survival (OS) of 37 mo. In low risk patients (age < 60 yrs and KPS ≥ 70) median OS was approximately 14 yrs. Survivors in CR a minimum of 2 yrs after diagnosis (n = 24) were evaluated with standard neuropsychological tests. Median follow-up was 12 yrs (range 2 to 26 yrs) and results indicated long-term preserved or improved cognitive function (Doolittle, J Clin Oncol 2013). Recently we compared efficacy from two first-line MTX-based regimens: HD MTX (intravenous, 4gr/m2) (Thiel, Lancet Oncol 2010), and enhanced BBB delivery of MTX (i.a., 3.5gr/m2). After adjusting for patient characteristics, CR rate and progression free survival were higher in patients < 65 yrs treated with enhanced delivery of MTX (p < 0.001). When first-line rituximab was added to the i.a. enhanced delivery regimen in 24 patients (median age 64 yrs; median KPS 65), the ORR improved to 92% (75% CR) and OS to 61 mo. To prevent recurrence, Ney (Leuk Lymphoma 2009) treated a small group of patients in CR after standard PCNSL treatment, with maintenance rituximab. The addition of maintenance immunotherapy resulted in average disease control of 22 mo or longer. Consistent with the Ney report, we noted prolonged median CR duration of 38 mo (range: 10 to 85 mo) in a small subset treated with maintenance rituximab (n = 9). Increased survival was also seen in translational laboratory studies of a rodent model of intracerebrally implanted MC116 human B-cell lymphoma cells, using single agent rituximab, whether or not delivered with BBB disruption and whether or not MTX was included (Muldoon, Clin Cancer Res 2011). These results suggest that rituximab slowly leaked into main CNS tumor mass even in absence of BBB opening; and given the long half-life, was trapped by binding to CD20+ on tumor cells, attaining sufficient concentration for antitumor efficacy. Our goal is to maximize first-line enhanced BBB delivery of SD chemotherapy to enable less treatment-related morbidity and mortality than is associated with HDC-ASCT in PCNSL, and increase CR duration. Neurocognitive safety has been demonstrated in long-term survivors treated with BBB delivery. Based on the encouraging results from Ney et al, our pilot data using maintenance rituximab, and translational lab studies of mAb delivery to brain, a new randomized multi-center trial is underway to study the effect of maintenance obinutuzumab on CR duration, neurocognition and quality of life in PCNSL patients who achieve CR following first-line MTX-based chemotherapy (NCT02498951). A trial update will be presented during the ASH 2016 meeting. Disclosures No relevant conflicts of interest to declare.

Clinical experience with oral vinorelbine (NVB) plus prednisone as first- or second-line chemotherapy of metastatic hormone- refractory prostate cancer (HRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16151-e16151
Author(s):  
J. M. Cervera ◽  
I. Garcia-Carbonero ◽  
R. Girones ◽  
M. Beltran ◽  
V. Calderero ◽  
...  
Keyword(s):  
Partial Response ◽  
Response Rate ◽  
Single Agent ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Psa Response ◽  
Line Chemotherapy ◽  
First Line Treatment

e16151 Background: IV NVB plus hydrocortisone (HC) compared with HC alone resulted in improved clinical benefit, progression-free survival (PFS) and PSA response rate in HRPC. The oral formulation of NVB avoids the side effects associated with the IV injection, may reduce administration and toxicity-related costs and is easy to administer. Due to these advantages, single agent oral NVB treatment could be considered as an optimal option for patients (p) with HRPC previously treated with a taxane or as first-line treatment when a taxane is not indicated. We retrospectively evaluated efficacy and toxicity or oral NVB administered as single agent as first or second-line chemotherapy of metastatic HRPC. Methods: Retrospectively data was collected from p with metastatic HRPC treated with oral NVB 80 mg/m2 days 1 and 8, with a prior test of myelosensitivity at 60 mg/m2 for the first cycle, plus prednisone 10 mg/day. Patients had received a taxane as first-line treatment or had a documented contraindication to receiving docetaxel. 1 cycle was equivalent to a 3-week period. Results: Data on 55 p treated in 11 Spanish centres were included for assessment. Median age was 72.5 years (range 54–86). ECOG PS 0, 17%; 1, 66%; 2, 17%. Median PSA 75 ng/mL. Prior taxane chemotherapy, 87%. Median number of cycles was 4 (range 1–6). 53.8% of p could escalate oral NVB to 80 mg/m2. 221 cycles were performed, 4.1% were delayed and 3.2% had a dose reduction. Grade 3–4 events were infrequent and mainly haematological: neutropenia (5.5% of p), anemia (3.6%), pain (3.6%), infection (1.8%), asthenia (1.8%), respiratory (1.8%). No febrile neutropenia was reported. 49 p were evaluable for PSA response rate; complete plus partial response was observed in 20.4% (95% CI: 10.2% - 34.3%) and PSA stable was reported in 40.8%. 29 p were evaluable for measurable disease; among them, 20.7% presented partial response and 44.8% stable disease. Median follow-up was 4.3 months. Survival status: 49 p (89.1%) are alive and 6 p (10.9%) died. Conclusions: Oral NVB is a safe and active regimen in previous chemotherapy treated HRPC. For those p who can not receive a taxane as first-line therapy, oral NVB can also be considered as an effective first-line treatment. No significant financial relationships to disclose.

Clinical experience with oral vinorelbine (NVBO) plus prednisone as first- or second-line chemotherapy of metastatic hormone-refractory prostate cancer (HRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15144-e15144
Author(s):  
Jose Manuel Cervera Grau ◽  
Miguel Beltran ◽  
Iciar Garcia Carbonero ◽  
Regina Girones ◽  
Aranzazu Gonzalez del Alba ◽  
...  
Keyword(s):  
Response Rate ◽  
Single Agent ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Oral Vinorelbine ◽  
Second Line Chemotherapy ◽  
Psa Response ◽  
Line Chemotherapy ◽  
First Line Treatment

e15144 Background: IV NVB plus hydrocortisone (HC) compared with HC alone resulted in improved clinical benefit, progression-free survival (PFS) and PSA response rate in HRPC. The oral formulation of NVB avoids the side effects associated with the IV injection, may reduce administration and toxicity-related costs and is easy to administer. Due to these advantages, single agent NVBO treatment could be considered as an optimal option for patients (p) with HRPC previously treated with a taxane or as first-line treatment when a taxane is not indicated. We retrospectively evaluated efficacy and toxicity or NVBO administered as single agent as first or second-line chemotherapy of metastatic HRPC. Methods: Retrospectively data was collected from p with metastatic HRPC treated with NVBO 80 mg/m2 on days 1 and 8, with a prior test of myelosensitivity at 60 mg/m2 for the 1st cycle (cy), plus prednisone 10 mg/day. Patients had received either a taxane as 1st-line treatment or had a documented contraindication to receiving docetaxel. 1 cy was equivalent to a 3-week period. Results: Data on 67 p treated in 13 Spanish centres were included. Median age 73 years (range 54-86). ECOG PS 0, 16.4%; 1, 56.7%; 2, 11.9%. Median PSA 88.9 ng/mL. Prior chemotherapy, 58.2%. Median number of cy was 4 (range 1-6). 56.9% of p could escalate NVBO to 80 mg/m2. 265 cy were performed, 9.1% were delayed and 2.3% had a dose reduction. Grade 3-4 events were infrequent and mainly hematological: neutropenia (6% of p), anemia (4.5%), pain (3%), infection (1.5%), asthenia (3%), respiratory (1.5%), cystitis (1.5%), rectal bleeding (1.5%), febrile syndrome (1.5%), renal (1.5%). No febrile neutropenia was reported. PSA response rate 16.1%, PSA stable was reported in 41.9%. 39 p were evaluable for measurable disease; among them, PR 17.9%, SD 48.7%. Median follow-up, 7.1 months. Median overall survival, 11 months [95% CI: 7.3-14.7]. Median PFS, 2.9 months [95% CI: 2.2-3.6]. Conclusions: NVBO is a safe and active regimen in previous chemotherapy treated HRPC. For those p who cannot receive a taxane as first-line therapy, NVBO can also be considered as an effective first-line treatment.

Is erlotinib for first-line use in EGFR+ non-small-cell lung cancer cost-effective?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19001-e19001 ◽  
Author(s):  
David L Veenstra ◽  
Preeti S. Bajaj ◽  
Josh John Carlson ◽  
Hans-Peter Goertz
Keyword(s):  
Lung Cancer ◽  
Cost Effective ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Life Years ◽  
Line Chemotherapy ◽  
First Line Treatment

e19001 Background: A recent phase III clinical trial, EURTAC, demonstrated that first-line treatment with erlotinib significantly improved progression-free survival (PFS) compared with standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients whose tumors harbored epidermal growth factor receptor (EGFR) mutations (Rosell 2012). We sought to estimate the cost-utility of treatment with erlotinib in this patient population from the US payer perspective. Methods: We developed a Markov model with three health states: PFS, progression, and death. Patients received treatment until progression, unacceptable toxicity or death; patients randomized to chemotherapy received a maximum of 4 treatment cycles. Transition probabilities were extrapolated from the trial. Median PFS was 9.7 months in patients receiving erlotinib and 5.2 months in patients receiving chemotherapy (p<0.0001). Cost and utility data were obtained from the literature. Probabilistic sensitivity analysis (PSA) was performed to assess uncertainty. We evaluated two scenarios: 1) first-line erlotinib vs. first-line chemotherapy, and 2) first-line erlotinib and mixed second-line treatments vs. first-line chemotherapy and second-line erlotinib. Results: First-line treatment with erlotinib vs. chemotherapy resulted in an increase of 0.60 life-years or 0.44 quality-adjusted life-years (QALYs). Mean total costs were $59,300 in the erlotinib arm and $17,800 in the chemotherapy arm, yielding an incremental cost-effectiveness ratio (ICER) of $98,338 with a 53% probability of being cost-effective at a willingness to pay (WTP) of $100,000/QALY. In the second scenario, the ICER was $50,002/QALY, with a 66% probability of being cost-effective. The main cost drivers in the model were the time spent in the PFS health state and drug costs. Conclusions: Treatment with erlotinib in first-line EGFR-positive NSCLC results in increased costs but also substantial increases in QALYs, demonstrating that this personalized approached to treatment may be cost-effective.

Impact of first-line cisplatin versus non-cisplatin based chemotherapy on progression-free survival in patients with advanced urothelial carcinoma previously treated with perioperative cisplatin based chemotherapy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 335-335
Author(s):  
Jennifer A Locke ◽  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Andrea Necchi ◽  
Patrizia Giannatempo ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Ecog Ps ◽  
Line Chemotherapy ◽  
First Line Treatment

335 Background: Perioperative cisplatin based chemotherapy (PCBC) is a standard of care in the management of muscle invasive urothelial carcinoma (UC). Cisplatin based (C) therapy also represents the historical first line treatment of metastatic disease. There is however no data to guide the optimal choice of first line chemotherapy regimen – C re-treatment vs other second-line or non cisplatin regimens (NC) –in UC patients who relapse after receiving PCBC. This multicenter retrospective study compares C vs NC first line treatment on progression-free survival (PFS) for patients (pts) with advanced UC after PCBC and cystectomy. Methods: Data were collected for patients who received various first-line chemotherapies for advanced UC following previous PCBC therapy. Cox proportional hazards models were used to investigate the prognostic ability of type of peri-operative / first-line chemotherapy, visceral metastasis, ECOG status, time from prior chemotherapy (TFPC), anemia, leukocytosis and albumin on PFS. Results: Data were available for 145 pts from 12 centers. The mean age was 62 years, 113 (77.9%) were men and ECOG-PS was 0 or >0 in 74 (51.0%) and 61 (42.0%) patients. Ninety-one (62.8%) pts received C first line, the median number of cycles was 4 (range 1-17) and the median TFPC was 6.2 months (range 1-154). Median overall survival was 86 weeks (95% CI 70-106) and median PFS was 24 (95% CI 18-27) weeks. Time from perioperative chemotherapy (TFPC) (>52 weeks vs ≤52 weeks; HR 0.63 p=0.027) and ECOG-PS at first line (1+ vs 0; HR 1.73 p=0.010), were prognostic of PFS. No significant effect was noted for C vs NC first line (p=0.70); however, among patients with TFPC >52 weeks, patients with NC had worse PFS (median 4.6 months, 95% CI 1.8-12.2) than those who received C (median 8.1, 95% CI 3.2-16.3). Conclusions: There is no evidence to suggest overall superiority of C vs NC based first line chemotherapy or a second-line regimen in patients with advanced UC who received prior PCBC. However, those with TFPC >52 weeks should probably receive C first line chemotherapy given better PFS with C.

Clinical Outcomes of Three or More Courses of First-line Chemotherapy for Metastatic Urothelial Carcinoma

2021 ◽  
Vol 1 (5) ◽  
pp. 459-461
Author(s):  
SHOHEI KAWAGUCHI ◽  
KOUJI IZUMI ◽  
RENATO NAITO ◽  
SUGURU KADOMOTO ◽  
HIROAKI IWAMOTO ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Urothelial Carcinoma ◽  
Focal Therapy ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Metastatic Urothelial Carcinoma ◽  
Line Drug ◽  
Line Chemotherapy ◽  
First Line Treatment

Background/Aim: The current standard of care for first-line treatment of locally advanced or metastatic urothelial carcinoma (UC) is platinum-based combination chemotherapy. Recently, immune checkpoint inhibitors have been reported to be effective for UC. Knowing whether immunotherapy or chemotherapy is suitable as first-line treatment is beneficial for patients. A retrospective study was conducted on the clinical outcomes of Japanese patients who received three or more courses of first-line chemotherapy for metastatic UC to assess the outcome of conventional treatments in real clinical situation. Patients and Methods: Patients who received first-line chemotherapy between August 2009 and December 2019 were included. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: The median PFS and OS were 7.1 and 27.1 months, respectively, for patients with no disease progression at the end of three courses. Of 28 patients, 25 (89.3%) received second-line drug therapy and 10 (35.7%) received focal therapy for disease control. Patients with focal therapy had significantly longer OS than those without focal therapy (p=0.019, log-rank test). Conclusion: OS of metastatic UC at our Institution is relatively long, suggesting that aggressive second-line drug therapy and focal therapy may have contributed to such result.

Sign in / Sign up

Export Citation Format

Share Document