Alternating anti-prion regimens reduce combination drug resistance but do not further extend survival in scrapie-infected mice

2021 ◽  
Vol 102 (12) ◽  
Author(s):  
Kathryn S. Beauchemin ◽  
Judy R. Rees ◽  
Surachai Supattapone
Keyword(s):  
Drug Resistance ◽  
Prion Diseases ◽  
Disease Free Survival ◽  
Combination Drug ◽  
Free Survival ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Combination Regimens ◽  
Disease Free

Prion diseases are fatal and infectious neurodegenerative diseases in humans and other mammals caused by templated misfolding of the endogenous prion protein (PrP). Although there is currently no vaccine or therapy against prion disease, several classes of small-molecule compounds have been shown to increase disease-free incubation time in prion-infected mice. An apparent obstacle to effective anti-prion therapy is the emergence of drug-resistant strains during static therapy with either single compounds or multi-drug combination regimens. Here, we treated scrapie-infected mice with dynamic regimens that alternate between different classes of anti-prion drugs. The results show that alternating regimens containing various combinations of Anle138b, IND24 and IND116135 reduce the incidence of combination drug resistance, but do not significantly increase long-term disease-free survival compared to monotherapy. Furthermore, the alternating regimens induced regional vacuolation profiles resembling those generated by a single component of the alternating regimen, suggesting the emergence of strain dominance.

1461: Local Control and Long Term Disease Free Survival Following Radical Prostatectomy for D1 Prostate Cancer In The PSA ERA

2004 ◽  
Vol 171 (4S) ◽  
pp. 385-385 ◽  
Author(s):  
Carl K. Gjertson ◽  
Kevin P. Asher ◽  
Joshua D. Sclar ◽  
Aaron E. Katz ◽  
Erik T. Goluboff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Local Control ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study.

1991 ◽  
Vol 9 (4) ◽  
pp. 581-591 ◽  
Author(s):  
A T Look ◽  
F A Hayes ◽  
J J Shuster ◽  
E C Douglass ◽  
R P Castleberry ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Gene Amplification ◽  
Gene Copy Number ◽  
Disease Free Survival ◽  
Gene Copy ◽  
Early Treatment Failure ◽  
Free Survival ◽  
Myc Gene ◽  
Disease Free

We assessed tumor cell DNA content (ploidy) and N-myc gene copy number as predictors of long-term disease-free survival in 298 children with neuroblastoma. Diploid tumor stem lines were identified in 101 patients (34%), clonal hyperdiploid abnormalities in 194 (65%), and hypodiploid stem lines in three (1%). In children with widely disseminated tumors at diagnosis (stage D), ploidy had a highly age-dependent influence on prognosis. Among infants (less than 12 months) treated with cyclophosphamide-doxorubicin, hyperdiploidy was closely associated with long-term disease-free survival (greater than 90% of cases), while diploidy invariably predicted early treatment failure (P less than .001). Similarly, in children 12 to 24 months of age who were treated with cisplatin-teniposide and cyclophosphamide-doxorubicin, diploidy uniformly predicted early failure, whereas half of the children with hyperdiploidy achieved long-term disease-free survival (P less than .001). There was no relationship between ploidy and treatment outcome in children older than 24 months with stage D tumors who had a very low probability of long-term disease-free survival (less than 10%). N-myc gene amplification was detected in 37 (25%) of the 147 tumors tested, with the remainder showing single-copy levels of the gene. N-myc gene amplification was more frequent in diploid than in hyperdiploid tumors (23 of 57 v 14 of 87, P = .001) and predicted a high likelihood of early treatment failure. In children younger than 2 years with disseminated neuroblastoma, tumor cell ploidy and N-myc gene copy number provide complementary prognostic information that will distinguish patients who can be cured on current regimens from those who require new treatment strategies.

scholarly journals Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Luminal Breast Cancer ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Disease Free

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

scholarly journals Long-term disease-free survival in acute nonlymphocytic leukemia

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1144-1147
Author(s):  
BA Peterson ◽  
CD Bloomfield
Keyword(s):  
Complete Remission ◽  
Induction Chemotherapy ◽  
Median Survival ◽  
Cytosine Arabinoside ◽  
Disease Free Survival ◽  
Acute Nonlymphocytic Leukemia ◽  
Maintenance Chemotherapy ◽  
Free Survival ◽  
Disease Free

Twenty-six of 45 adults (58%) with acute nonlymphocytic leukemia who were treated with intensive induction chemotherapy over 5 yr ago entered complete remission. All patients entering remission were placed on weekly maintenance chemotherapy consisting of cytosine arabinoside and 6-thioguanine. The median duration of complete remission was 17 mo and 7 patients (27%) remained in their initial remission for 62 + to 102 + mo. All but one of the patients in complete remission over 5 yr have had treatment discontinued. Only 1 of 7 patients in remission for more than 5 yr has relapsed. Median survival is 26.5 mo, and 8 patients (31%) currently remain alive without evidence of leukemia 63--105 mo from diagnosis. It is possible to achieve long-term disease-free survival with chemotherapy alone in acute nonlymphocytic leukemia.

Long-Term Outcomes and Factors Related to the Prognosis of Pure Ovarian Dysgerminoma: A Retrospective Study of 107 Cases

2021 ◽  
pp. 1-8
Author(s):  
Tianyun Xu ◽  
Fei Sun ◽  
Yanfang Li
Keyword(s):  
Retrospective Study ◽  
Survival Rate ◽  
Disease Free Survival ◽  
Small Sample ◽  
Stage I ◽  
Long Term Outcomes ◽  
Free Survival ◽  
Disease Free Survival Rate ◽  
Disease Free

<b><i>Objective:</i></b> The aim of this study was to evaluate the long-term outcomes and the factors related to patient prognosis. <b><i>Materials and Methods:</i></b> We retrospectively analyzed patients treated at the Department of Gynecology, Sun Yat-sen University Cancer Center, between January 1, 1968, and December 12, 2018. <b><i>Results:</i></b> A total of 107 patients were identified. Of all patients, 79 (73.8%) presented with stage I disease, 14 (13.1%) stage II, 13 (12.2%) stage III, and 1 (0.9%) stage IV. All patients received surgery, with 70 (65.4%) undergoing fertility-sparing surgery (FS) and 37 (34.6%) nonfertility-sparing surgery (NFS). Ninety patients received postoperative chemotherapy. Nine of the 43 cases with a lymphadenectomy had metastasis (20.9%). The median follow-up time was 132 months (range, 1–536 months). The overall 5-year and 10-year survival was 95.1% and 91.7%, respectively. The 10-year survival rate for stage I and II–IV patients was 96.1% and 79.1%, respectively (<i>p</i> = 0.008). For the patients undergoing FS and NFS, the 10-year disease-free survival rate was 82.3% and 88.0%, respectively (<i>p</i> = 0.403). The 10-year disease-free survival rate for patients with or without lymphadenectomy was 95.1% and 78.4%, respectively (<i>p</i> = 0.040), and it was 92.5% and 76.0%, respectively (<i>p</i> = 0.041), for those with or without omentectomy. Fifteen patients relapsed, and 4 of them (26.7%) had recurrence in the lymph nodes. Eleven of the 15 relapsed patients (73.3%) had been successfully salvaged. <b><i>Limitations:</i></b> As a study of a rare disease, our analysis was limited by its small sample size and the deemed disadvantage of a retrospective study. <b><i>Conclusion:</i></b> Excellent treatment results can be achieved in dysgerminoma patients who received proper treatment. Lymphadenectomy may improve patient survival. Relapsed patients can also be successfully salvaged.

Retinoblastoma

2020 ◽  
pp. 270-276
Author(s):  
Guillermo Chantada ◽  
Carlos Rodríguez-Galindo
Keyword(s):  
Disease Free Survival ◽  
Developed Countries ◽  
Germline Mutations ◽  
Secondary Malignancies ◽  
Rb1 Gene ◽  
Free Survival ◽  
Intravitreal Chemotherapy ◽  
Disease Free Survival Rate ◽  
Disease Free

Retinoblastoma is the most common paediatric ocular malignancy. Its disease-free survival rate in developed countries is higher than 95%, but in the developing world this tumour presents with advanced disease leading to poorer outcome. Late diagnosis and problems with compliance for treatment affect the outcome in that setting. Retinoblastoma may occur in children with germline mutations of the RB1 gene, who usually present with bilateral heritable disease. In those with somatic mutations, it always presents as unilateral and non-hereditable disease. The former have a higher susceptibility for secondary malignancies occurring later in life. Enucleation of the affected eyeball is often curative when the disease presents intraocularly, but conservative therapies have evolved from conventional external photon-beam radiotherapy, which was associated with severe long-term toxicity, to chemotherapy plus local treatments. Recently, local intra-arterial and intravitreal chemotherapy has been more intensively used, leading to higher preservation rates.

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