scholarly journals Modeling long-term health outcomes of patients with cystic fibrosis homozygous for F508del-CFTR treated with lumacaftor/ivacaftor

2019 ◽  
Vol 13 ◽  
pp. 175346661882018 ◽  
Author(s):  
Jaime L. Rubin ◽  
Lasair O’Callaghan ◽  
Christopher Pelligra ◽  
Michael W. Konstan ◽  
Alexandra Ward ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Health Outcomes ◽  
Median Survival ◽  
Patient Simulation ◽  
Simulation Models ◽  
Patient Characteristics ◽  
Model Parameters ◽  
Term Survival ◽  
Lifetime Treatment

Background: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quantified. Simulation models can provide predictions about long-term health outcomes. In this study, we aimed to project long-term health outcomes of LUM/IVA plus standard care (SC) in patients with CF homozygous for F508del-CFTR. Methods: This modeling study was an individual patient simulation in US patients aged ⩾6 years with CF, homozygous for F508del-CFTR. The primary outcome was projected survival among (a) a cohort of patients who ever initiated LUM/IVA, accounting for treatment discontinuations, and (b) a cohort of patients who remain on continuous LUM/IVA. Patient characteristics and model parameters were derived from clinical trials: VX14-809-109, VX13-809-011B, TRAFFIC/TRANSPORT, and PROGRESS; published literature; and the US CF Foundation Patient Registry. Results: Lumacaftor/ivacaftor + SC is expected to increase median survival by 6.1 years versus SC alone, accounting for treatment discontinuations. The incremental median predicted survival versus SC assuming initiation of LUM/IVA at ages 6, 12, 18, and 25 years was 17.7, 12.6, 8.0, and 3.8 years, respectively. Assuming lifetime treatment with LUM/IVA, incremental median survival was predicted to be 7.8 years longer in the LUM/IVA + SC cohort. Initiating LUM/IVA at ages 6, 12, 18, and 25 years and assuming lifetime treatment resulted in incremental median predicted survival of 23.4, 18.2, 11.0, and 4.8 years, respectively. Conclusions: Lumacaftor/ivacaftor is projected to increase survival for patients with CF. Initiation at an early age and treatment persistence result in further increments in projected survival.

EXTH-13. LOCAL DELIVERY OF AN IL-15 SUPERAGONIST USING A REPLICATING RETROVIRUS SIGNIFICANTLY IMPROVES SURVIVAL AND LYMPHOCYTE INFILTRATION IN POORLY IMMUNOGENIC MURINE GLIOBLASTOMA MODELS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi166-vi166
Author(s):  
Alexander Haddad ◽  
Jordan Spatz ◽  
Megan Montoya ◽  
Sara Collins ◽  
Sabraj Gill ◽  
...  
Keyword(s):  
T Cell ◽  
Median Survival ◽  
T Cell Activation ◽  
Term Survival ◽  
Long Term Survival ◽  
Immunosuppressive Cell ◽  
Imaging Results ◽  
Local Immunosuppression ◽  
Inflammatory Changes

Abstract Glioblastoma (GBM) leads to severe systemic and local immunosuppression, and immunotherapies have had limited clinical success. Here, we evaluated the treatment efficacy of RLI, a superagonist of T-cell activator IL-15, delivered to tumor cells using a tumor-selective retroviral replicating vector (RRV) in the syngeneic murine SB28 and Tu2449 GBM models, which are both engineered to be poorly immunogenic with low-mutational burden and known resistance to immunotherapy, and hence more accurate biomimetic models of human GBM. RRV-RLI replicated and spread effectively in cultured murine GBM cells with robust production of functional RLI (165.4 ± 5.3 ng/mL). Stereotactic injection of RRV-RLI into pre-established intracerebral SB28 tumors significantly reduced tumor growth on bioluminescent imaging, and increased median survival compared to control mice (55 vs. 19 days, p=0.002), leading to long-term survival in 12% of treated mice. In the Tu2449 model, imaging results showed complete eradication of intracerebral tumors after RRV-RLI treatment, with long-term survival (median not reached) in > 85% of treated mice, compared to a median survival of 12.5 days in control mice (p=0.001). RRV-RLI treated tumors showed significantly increased CD8 T-cell infiltration, without altering immunosuppressive cell populations. Similarly, broad anti-tumor inflammatory changes, including increased expression of genes involved in T-cell activation and killing, were observed in the NanoString nCounter platform using a 770-gene panel representing various immune cell types. Notably, RLI was not detected in the blood of treated mice, and tumor-localized RRV-RLI gene delivery showed no adverse systemic immune effects in either model. In summary, RRV-mediated RLI immunotherapy results in immunostimulatory and pro-inflammatory changes to the tumor microenvironment and achieves a significant survival benefit in two poorly immunogenic syngeneic murine models of GBM. This tumor-localized immunomodulatory gene therapy has the potential to safely reverse the T-cell depleted immunophenotype of GBM.

Peritoneal Colorectal Carcinomatosis Treated With Surgery and Perioperative Intraperitoneal Chemotherapy: Retrospective Analysis of 523 Patients From a Multicentric French Study

2010 ◽  
Vol 28 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Dominique Elias ◽  
François Gilly ◽  
Florent Boutitie ◽  
François Quenet ◽  
Jean-Marc Bereder ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Median Survival ◽  
Intraperitoneal Chemotherapy ◽  
Combined Treatment ◽  
Prognostic Impact ◽  
Term Survival ◽  
Multicentric Study ◽  
Long Term Survival ◽  
French Speaking

Purpose Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. Patients and Methods A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. Conclusion This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.

Relapse Rate and Long-Term Survival of AL Amyloidosis Patients Treated with High-Dose Melphalan and Autologous Stem Cell Transplantation (HDM/SCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3094-3094
Author(s):  
David C. Seldin ◽  
Martha Skinner ◽  
Betul Oran ◽  
Karen Quillen ◽  
Kathleen T. Finn ◽  
...  
Keyword(s):  
Median Survival ◽  
Plasma Cell ◽  
Relapse Rate ◽  
Long Term Results ◽  
High Dose ◽  
Al Amyloidosis ◽  
Term Survival ◽  
Long Term Survival ◽  
Early Results

Abstract AL amyloidosis is a plasma cell dyscrasia in which clonal immunoglobulin light chains misfold and are deposited in tissues, leading to organ failure in untreated patients, with median survival of only ~1 year. Oral melphalan and prednisone is minimally effective for the disease, with an increase in median survival to ~1.5 years, and a low rate of hematologic complete responses (CRs). Twelve years ago, we began treating patients with AL amyloidosis with HDM/SCT. In the plasma cell malignancy multiple myeloma, this approach produces hematologic CRs and improves survival, but is not curative, as all patients eventually relapse. In AL amyloidosis, the relapse rate and long-term survival have not been studied, but early results are promising, with most centers reporting CR rates of ~40% and excellent survival in responding patients. To address the durability and long-term results of treatment with HDM/SCT, here we report on the outcome for AL amyloidosis patients treated at Boston Medical Center with HDM/SCT >10 years ago. The first autologous transplant took place on July 18, 1994 in two years, by July 18, 1996, 43 patients with AL amyloidosis without myeloma or other hematologic disease had been treated with HDM/SCT, receiving 100–200 mg/m2 melphalan depending upon age and protocol. Of the 43 patients treated in this 2 yr period, 76% of the patients were male, 81% had a lambda monoclonal disease, and their median age was 52 (range, 29–71). In these first 43 patients, the 100 day peri-transplant mortality rate was 16%. Nineteen of the 43 patients (44%) achieved a hematologic CR after treatment. In annual followup, 4 of 19 patients (21%) eventually relapsed. Fourteen of 43 patients (33%) are still alive; 12 of 19 patients who achieved a CR (63%) are still alive, while only 2 of 34 patients who did not (6%) are still alive. Although there were fewer (8) patients with kappa clonal disease, they had a better outcome, with an 87% CR rate vs. 34% for lambda (P=0.006); 75% of the kappa patients are still alive, vs. 23% of the lambda patients (P=0.005). The median survival of all 43 patients is 4.7 years. Thus, treatment of AL amyloidosis patients with HDM/SCT produces a high CR rate that is durable and is associated with excellent 10 year survival, particularly for those patients achieving a hematologic CR and for patients with kappa clonal disease. Ongoing clinical trials of HDM/SCT, along with strategies to reduce morbidity and mortality and to improve the CR rate, incorporating additional cycles of HDM/SCT or new anti-plasma cell agents, appear to be well-justified by these results.

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

MR-guided laser-induced thermotherapy (LITT) in liver metastases of colorectal cancer: Long-term survival data.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14131-e14131
Author(s):  
Thomas J. Vogl ◽  
Alena Dommermuth ◽  
Katrin Eichler ◽  
Stephan Zangos
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Survival Rate ◽  
Lymph Nodes ◽  
Liver Metastases ◽  
Median Survival ◽  
Cox Regression ◽  
Term Survival ◽  
Median Survival Rate

e14131 Background: To evaluate retrospectively long-term survival of 594 patients with colorectal liver metastases treated with MR-guided laser-induced thermotherapy (LITT) depending on different factors. Methods: 594 patients with liver metastases from colorectal carcinoma treated with MR-guided LITT between 01/99 and 12/10 were included. For survival analysis tumor localization, TNM classification, number of metastases, diameter and volume of metastases and necrosis, lobular spread, number of treatment sessions, performance of adjuvant chemotherapy and transarterial chemoembolisation were considered. The Kaplan-Meier method was used to conduct this survival analysis. Results: Log-rank test showed statistically significant differences between survival curves, multivariate Cox-regression-analysis (p<0.05) showed prognostic factors regarding overall survival like number of metastases pre intervention, adjuvant chemotherapy, diameter of metastases, ratio of volumes of necrosis and metastases, and affected lymph nodes. Median overall survival rate at the time of first LITT was 25 months, 1-year survival: 78%, 2-year survival: 50.1%, 3-year survival: 28%; 4-year survival: 16.4%; 5-year survival: 7.8%. Numbers of metastases pre intervention: 1-2 metastases with a median survival rate of 60 months; 3-4 metastases: 45 months; ≥5 metastases: 42 months. Median survival rate for metastases <20mm in diameter 36 months; 20-30mm 27 months, 30-40mm 24 months and >40mm 21 months. Affected lymph nodes: median survival rate for patients with N0-classification 30 months, N1-classification 24 months; N2/N3/N4-classification 22 months. Conclusions: Multivariate Cox regression model provided the minimal number of significant variables with the maximal prognostic value concerning overall survival for MR-guided LITT, i.e., diameter and number of metastases and primary classification of lymph nodes.

Long-term survival in patients with peritoneal metastasized gastric cancer treated with cytoreductive surgery and HIPEC: A multi-institutional cohort from PSOGI.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 390-390
Author(s):  
Andreas Brandl ◽  
Yutaka Yonemura ◽  
Olivier Glehen ◽  
Paul H. Sugarbaker ◽  
Beate Rau
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Median Survival ◽  
Cytoreductive Surgery ◽  
Peritoneal Metastasis ◽  
Tumor Recurrence ◽  
Term Survival ◽  
Long Term Survival ◽  
Crs And Hipec

390 Background: Peritoneal metastasis of gastric cancer is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in median survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyze a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics. Methods: We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven peritoneal metastasis of gastric cancer, treated with CRS and HIPEC, and overall survival > 5 years. Patient, tumor, and therapeutic details were collected and analyzed. Results: A total of 29 patients with a mean age of 52.5 years and a mean PCI of 3.2 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and low PCI (PCI < 6) were present in 23/29 patients. 13/29 patients developed at a median of 82.2 months tumor recurrence. Tumor recurrence was associated with inferior median overall survival compared to patients without tumor recurrence (8.8 years vs. not reached; p = 0.002). Conclusions: Long-term survival and even cure are possible in patients with peritoneal metastasis of gastric cancer treated with CRS and HIPEC. Completeness of cytoreduction (CC-0) and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.

scholarly journals Long-Term Survival after Gamma Knife Radiosurgery in a Case of Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Sudheer R. Thumma ◽  
Ameer L. Elaimy ◽  
Nathan Daines ◽  
Alexander R. Mackay ◽  
Wayne T. Lamoreaux ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Median Survival ◽  
Gamma Knife Radiosurgery ◽  
Recurrent Glioblastoma ◽  
Initial Diagnosis ◽  
External Beam Radiation ◽  
Unique Case ◽  
Beam Radiation ◽  
Term Survival

The management of recurrent glioblastoma is highly challenging, and treatment outcomes remain uniformly poor. Glioblastoma is a highly infiltrative tumor, and complete surgical resection of all microscopic extensions cannot be achieved at the time of initial diagnosis, and hence local recurrence is observed in most patients. Gamma Knife radiosurgery has been used to treat these tumor recurrences for select cases and has been successful in prolonging the median survival by 8–12 months on average for select cases. We present the unique case of a 63-year-old male with multiple sequential recurrences of glioblastoma after initial standard treatment with surgery followed by concomitant external beam radiation therapy and chemotherapy (temozolomide). The patient was followed clinically as well as with surveillance MRI scans at every 2-3-month intervals. The patient underwent Gamma Knife radiosurgery three times for 3 separate tumor recurrences, and the patient survived for seven years following the initial diagnosis with this aggressive treatment. The median survival in patients with recurrent glioblastoma is usually 8–12 months after recurrence, and this unique case illustrates that aggressive local therapy can lead to long-term survivors in select situations. We advocate that each patient treatment at the time of recurrence should be tailored to each clinical situation and desire for quality of life and improved longevity.

Predictors of Long Term Survival in Patients With Cystic Fibrosis Following Lung Transplantation

2018 ◽  
Vol 37 (4) ◽  
pp. S446
Author(s):  
C.A. Robinson ◽  
A. Deibel ◽  
M.M. Schuurmans ◽  
I. Inci ◽  
C. Benden
Keyword(s):  
Cystic Fibrosis ◽  
Lung Transplantation ◽  
Term Survival ◽  
Long Term Survival
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