scholarly journals Total Diagnostic Delay in Oral Cancer may be Related to Advanced Disease Stage at Diagnosis

2012 ◽  
Vol 12 (2) ◽  
pp. 84-86 ◽  
Author(s):  
Jennifer L. Cleveland ◽  
Gina Thornton-Evans
Keyword(s):  
Oral Cancer ◽  
Advanced Disease ◽  
Diagnostic Delay ◽  
Disease Stage ◽  
Stage At Diagnosis ◽  
Advanced Disease Stage

Nephrotoxicity in patients with cancer treated with immune checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14558-e14558
Author(s):  
Evangelos Eleutherakis Papaiakovou ◽  
Efstathios Kastritis ◽  
Flora Zagouri ◽  
Dimitra Grapsa ◽  
Ioannis Ntanassis-Stathopoulos ◽  
...  
Keyword(s):  
Renal Function ◽  
Immune Checkpoint ◽  
Impaired Renal Function ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Disease ◽  
Checkpoint Inhibitors ◽  
Disease Stage ◽  
Clinicopathological Parameters ◽  
Stage At Diagnosis ◽  
Advanced Disease Stage

e14558 Background: Despite their efficacy in various cancer types, administration of immune checkpoint inhibitors (ICIs) may be complicated by the development of immune-related adverse events (IrAE). Nephrotoxicity represents a relatively rare but clinically significant adverse event, associated with the administration of ICI. Methods: The medical records of 294 patients with solid tumors or hematological malignancies that received ICIs for at least 4 weeks were retrospectively reviewed. Demographic, clinicopathological, treatment, toxicity and outcome data were recorded. ICI-associated nephrotoxicity was correlated with the remaining clinicopathological parameters as well as with progression-free survival (PFS) and overall survival (OS). Results: The majority of patients were male (70.4%), with bladder cancer or renal cell carcinoma (38.1% and 27.6%, respectively), and stage IV disease (56.8%), and had received ICI as monotherapy (68,7%). Nephrotoxicity during immunotherapy administration was observed in 20/ 294 (6.8%) patients, was mild (grade 1) and reversible in 55% and 75% of these cases, respectively, and was significantly associated with nephrotoxicity from previously administered therapy (p = 0,008), impaired renal function at initiation of ICIs (p = 0.044). and advanced disease stage at diagnosis (p = 0,028). No correlation between ICI-nephrotoxicity and PFS or OS was observed. Conclusions: ICI-associated nephrotoxicity was a relatively infrequent IrAE in our patient population, most commonly mild and reversible, and with no significant effect on survival. Preexisting treatment-related nephrotoxicity, impaired renal function and/or advanced disease stage at diagnosis may represent significant predisposing factors for its development.

The use of insulin and the effect on survival of non-small cell lung cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22073-e22073
Author(s):  
S. Y. Farhan ◽  
M. Jankowski ◽  
A. Hanbali ◽  
D. Wang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Advanced Disease ◽  
Small Cell ◽  
Disease Stage ◽  
Diabetic Patients ◽  
Stage At Diagnosis ◽  
Small Cell Lung ◽  
Cancer Specific Survival ◽  
Advanced Disease Stage

e22073 Background: Diabetes mellitus (DM) is one of the common morbidities in United States. Insulin therapy has been frequently used in its treatment. Some studies have postulated that activation of Insulin and Insulin-like growth factor (IGF) pathway may contribute to cancer proliferation, growth and resistance to anticancer therapies. The impact of insulin on diabetic patients with non-small cell lung cancer (NSCLC) has not been reported. Methods: 1,233 patients with NSCLC diagnosed between January 1999 and December 2004 were identified from the Tumor Registry at Henry Ford Health System. Based on inclusion criteria, data from 1,206 patients were extracted from the electronic medical records. Statistical analyses were performed between insulin and non insulin users. Results: Out of 1,206 patients, 193 patients had NSCLC and DM. Data was available from 192 patients. Sixty (31.3%) were on insulin at the time of NSCLC diagnosis and defined as insulin users, while 132 were not on insulin and defined as non- users (68.7%). Demographics, co-morbidities, disease stage at diagnosis, therapeutic interventions, and laboratory values were analyzed for overall and cancer-specific survival. More insulin users (81%) than non-users (64%) presented with advanced disease (stage ≥ 3) at diagnosis (P=0.02). Although no significant difference of Hemoglobin A1c was observed, the median survival from all causes of death was 6.5 months for insulin-users versus 9.9 months for non-users (P=0.08). When survival time was calculated from cancer-specific death, the median survival between insulin and non-insulin users was 7.2 months versus 38.7 months, respectively (P=0.002), with a hazard ratio (HR) for insulin use equals 1.91. Results from our univariable and multivariable analyses will be presented at the ASCO annual meeting in detail. Conclusions: This data indicates that the use of insulin may adversely affect the biology and clinical course of NSCLC with a tendency of advanced disease stage at diagnosis and a shorter cancer-specific survival time. Prospective study of DM with NSCLC or other cancer diagnosis will improve our understanding of this potential adverse effect on cancer biology and provide scientific rational to target IGF-pathway especially in diabetic patients. No significant financial relationships to disclose.

scholarly journals Loss of cIAP1 in Endothelial Cells Limits Metastatic Extravasation through Tumor-Derived Lymphotoxin Alpha

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 599
Author(s):  
Lazaros Vasilikos ◽  
Kay Hänggi ◽  
Lisanne M. Spilgies ◽  
Samanta Kisele ◽  
Stefanie Rufli ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Advanced Disease ◽  
Disease Stage ◽  
Stromal Compartment ◽  
Tumor Load ◽  
Smac Mimetics ◽  
Advanced Disease Stage ◽  
Lymphotoxin Alpha ◽  
Open Question

In this study, we determined whether Smac mimetics play a role in metastasis, specifically in circulation, tumor extravasation and growth in a metastatic site. Reports suggest inducing the degradation of IAPs through use of Smac mimetics, alters the ability of the tumor cell to metastasize. However, a role for the immune or stromal compartment in affecting the ability of tumor cells to metastasize upon loss of IAPs has not been defined. To address this open question, we utilized syngeneic tumor models in a late-stage model of metastasis. Loss of cIAP1 in the endothelial compartment, rather than depletion of cIAP2 or absence of cIAP1 in the hematopoietic compartment, caused reduction of tumor load in the lung. Our results underline the involvement of the endothelium in hindering tumor cell extravasation upon loss of cIAP1, in contrast to the immune compartment. Endothelial specific depletion of cIAP1 did not lead to cell death but resulted in an unresponsive endothelium barrier to permeability factors causing a decrease in tumor cell extravasation. Surprisingly, lymphotoxin alpha (LTA), and not TNF, secreted by the tumor cells, was critical for the extravasation. Using TCGA, we found high LTA mRNA expression correlated with decreased survival in kidney carcinoma and associated with advanced disease stage. Our data suggest that Smac mimetics, targeting cIAP1/2, reduce metastasis to the lung by inhibiting tumor cell extravasation.

Malignant mesothelioma: prognostic variables in a registry of 180 patients, the Dana-Farber Cancer Institute and Brigham and Women's Hospital experience over two decades, 1965-1985.

1988 ◽  
Vol 6 (1) ◽  
pp. 147-153 ◽  
Author(s):  
K Antman ◽  
R Shemin ◽  
L Ryan ◽  
K Klegar ◽  
R Osteen ◽  
...  
Keyword(s):  
Chest Pain ◽  
Advanced Disease ◽  
Performance Status ◽  
Randomized Study ◽  
Prolonged Survival ◽  
Disease Stage ◽  
Computer Search ◽  
Prognostic Variables ◽  
Dana Farber Cancer Institute ◽  
Advanced Disease Stage

All mesothelioma patients identified by a computer search of pathologic diagnoses at the Dana-Farber Cancer Institute (DFCI) between 1965 and 1985 were the subjects of this analysis. A total of 180 patients were identified, 136 with pleural and 37 with peritoneal mesothelioma. There were five pericardial and two testicular primaries. Of the two decades included in the study, later patients were significantly older, with a more advanced disease stage, and a lower performance status than those accrued early in the study. Factors at diagnosis associated with a significantly prolonged survival for all patients with mesothelioma included a 0 to 1 performance status, absence of chest pain, age less than 50 years, and epithelial histology. Factors at diagnosis associated with prolonged survival for the subset of patients with pleural mesothelioma included epithelial histology, 0 to 1 performance status, the absence of chest pain, an interval of greater than 6 months from onset of symptoms, and treatment with chemotherapy and pleuropneumonectomy. This last result must be interpreted with caution, since this was not a randomized study.

scholarly journals T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy

2020 ◽  
Author(s):  
Pascal Martin ◽  
Gisela E. Hagberg ◽  
Thomas Schultz ◽  
Klaus Harzer ◽  
Uwe Klose ◽  
...  
Keyword(s):  
Metachromatic Leukodystrophy ◽  
Advanced Disease ◽  
Magnetization Transfer ◽  
Brain Magnetic Resonance Imaging ◽  
Disease Stage ◽  
Magnetization Transfer Ratio ◽  
Water Fraction ◽  
Mri Protocol ◽  
Advanced Disease Stage ◽  
Multimodal Mri

Abstract Purpose T2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course. Methods The volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5–5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping. Results T2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity. Conclusion In late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.

Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Myelodysplastic Syndromes 50 Years or Older. A Retrospective Survey from the EBMT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 520-520 ◽  
Author(s):  
ZiYi Lim ◽  
Ronald Brand ◽  
Anja van Biezen ◽  
Jurgen Finke ◽  
Dietger W. Niederwieser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Advanced Disease ◽  
Disease Stage ◽  
Hematopoietic Stem ◽  
Donor Type ◽  
Advanced Disease Stage

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with MDS. However, the advanced age of the majority of patients with MDS poses a significant barrier to the success of transplantation. Many of these patients have co-morbidities, or lack a suitable sibling matched donor. While reduced intensity conditioning (RIC) has expanded the scope of allografting to older patients, it remains unclear as to whether it confers an improvement in overall survival in this patient sub-group. Here we report on the results of a retrospective multi-centre analysis of 1385 patients aged 50 years or older with MDS transplanted since 1993. The main variables analysed in this study were donor status (sibling vs unrelated matched), age group (50–60 years vs >60years), disease stage at time of transplantation (early:<5% blasts vs advanced:>5% blasts), type of conditioning regimen (RIC vs standard myeloablative conditioning, SMC), period of transplantation (1993–96, 1997–2000–2001-). There were 1000 matched sibling (72%) and 385 matched unrelated donor transplants (28%). The median age of the cohort was 56 years (range:50–74 years), with 1053 patients (76%) aged 50–60 years and 332 patients (24%) above 60 years. 604 patients(44%) received SMC and 781 patients (56%) received RIC. 189 patients (14%) had RA/RARS, 388 patients (28%) had RAEB, 233 patients(17%) had RAEB-t and 393 patients secondary AML (28%). FAB classification was unavailable for 182 patients (13%). Patients receiving RIC were older (age>60 years: 30% RIC vs 14% SMC, p<0.001), but SMC had a more advanced disease stage at transplant (42% RIC vs 51% SMC). There was no difference in donor type between RIC and SMC (MUD: 28% RIC vs 28% SMC) The estimated cumulative incidence (competing risk model) at 4-years post transplant for TRM decreased from 47%(1993–1996), via 40%(1997–2000) to 35%(2001-); for Relapse Incidence these figures are 29%, 33% and 40% respectively. On multivariate analysis, age >60 years(HR:1.28, 95%CI [1.0–1.6], p=0.04), use of RIC (HR:1.50 95%CI [1.2–1.9], p<0.001) and advanced disease stage at transplantation (HR:1.51, 95%CI [1.2–2.0], p=0.002) were associated with an increased relapse rate; the use of RIC with a lower TRM (HR:0.71, 95%CI [0.57–0.88], p<0.01) and advanced disease stage at transplantation with a higher TRM (HR: 1.4, 95%CI [1.1–1.8], p<0.01) In contrast, donor type did not significantly influence either the 4-year TRM or relapse rates(HR’s 1.12 and 0.94 respectively, both p>0.30). Advanced disease stage at transplantation was the only independent variable associated with an inferior 4-year overall survival(OS)(HR: 1.47, 95%CI [1.2–1.8], p<0.001). In conclusion, disease stage at time of transplantation has an important prognostic impact on outcomes. The use of RIC is associated with higher relapse but lower TRM and comparable OS with SMC in this cohort. While patients aged >60 years had an increased relapse rate, there was no significant difference in OS compared with those aged 50–60 years. The choice of donor did not significantly influence outcomes. Long-term survival can be achieved in a sub-group of older MDS patients, but prospective studies are warranted to improve patient selection and to identify optimal treatment strategies.

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