Response Rate of 16% and High Incidence of Adverse Events In Placebo-Treated Patients with CD25 Assay-Positive Cutaneous T-Cell Lymphoma (CTCL): An Analysis of Patient Characteristics and Predictors of Response

Abstract Abstract 4158 Background: CTCLs are rare, extranodal non-Hodgkin's lymphomas characterized by the accumulation of malignant T lymphocytes in the skin; mycosis fungoides (MF) and Sézary syndrome (SS) are the most common variants. Their clinical course is typically chronic and progressive, despite multiple therapeutic interventions. Observational studies of patients with CTCL, although limited by rarity, are necessary to improve understanding of prognostic factors. Aims: The goals of this analysis were to describe the initial disease characteristics, prognostic factors, and natural history of disease observed in 44 patients with CD25-positive, recurrent/persistent CTCL included in the placebo arm of Study L4389-11. We were particularly interested to determine if there were any characteristics peculiar to the 16% of patients treated with placebo who were observed to have a response in this study. Methods: This multicenter, randomized, double-blind, placebo-controlled phase III trial compared 2 different doses of denileukin diftitox (9 or 18 μ g/kg/day) with placebo in 144 patients with histopathologically confirmed stage IA to III MF/SS who had received ≤3 previous therapies. Medications essential for patient welfare (cardiac medications, narcotics, anti-nausea agents, vitamins, or laxatives) and transfusions were also allowed. The primary efficacy endpoint was overall response rate (ORR); progression-free survival (PFS) was a secondary endpoint. Relationships between baseline covariates and clinical outcomes were assessed by multivariate regression analyses. Results: Placebo-treated patients had a median age of 59.0 years, and the majority were white (77.3%), had early-stage disease (stage <IIA; 68.2%), had a diagnosis of MF (84.1%), and had <20% circulating abnormal lymphocytes (85.4%) at baseline. The ORR was 15.9% (95% exact confidence interval [CI]: 6.6%-30.1%) for patients receiving placebo (complete response: 2.3%; partial response: 13.6%), reflecting a possible baseline rate of spontaneous disease remission expected in untreated CTCL. Of the 7 responding patients, 3 were treated during the trial with systemic anti-staphylococcal antibiotics (2 pts with IIB, 1pt with erythroderma). Of the remaining 4 pts the stages were 1A (1), IB (2), IIB (1). Median PFS according to Kaplan-Meier analysis was 124 days (4.1 months) (95% exact CI: 92–176 days (3.0-5.8 months)), and the median values for patients with stage ≤IIA disease and stage ≥IIB disease at baseline were 107 days (3.5 months) and 211 days (6.9 months), respectively. Multivariate analyses identified no significant effects of any baseline factors on either ORR or PFS, although there was a trend toward poorer PFS associated with advanced age (hazard ratio: 1.21; 95% CI: 0.97–1.52; P=.0947). These analyses were likely limited by small sample size. A total of 95.5% of patients in the placebo arm used rescue medications (skin moisturizers etc.) at least once during the treatment period. Adverse events (AEs) and treatment-related AEs occurred in 90.9% and 59.1% of placebo-treated patients, respectively. General disorders and administration site conditions were the most common types of treatment-related AEs (52.3%), which included fatigue (22.7%), rigors (15.9%), peripheral edema (15.9%), pyrexia (13.6%), and pain (2.3%). Sepsis occurred significantly more often with placebo versus active treatment (6.8% vs. 0%; P < .05). Three of the 7 (43%) responders had received systemic antibiotics and 14/37 non-responders had received systemic antibiotics (38%). Conclusion: The findings from this study demonstrate that responses can be observed in patients with MF/SS in the absence of anti-tumor treatment. Likely contributing factors to these ‘spontaneous responses' are the use of systemic antibiotics, aggressive ‘rescue medication' use and the waxing and waning nature of skin lesions, particularly in early-stage disease. All future studies should carefully document the use of systemic antibiotics during therapy. These results can serve as standard comparators for other active-treatment studies that lack a placebo control arm. Disclosures: Prince: Eisai: Consultancy, Honoraria. Duvic:Eisai: Consultancy, Research Funding, Speakers Bureau. Assaf:Eisai: Consultancy, Honoraria. Straus:Eisai: Consultancy, Honoraria.

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Expression of the Cancer-Testis Antigens, SEMG 1 and Protamine 1, in Early CLL: Their Relationship to Disease Stage and Zap 70 Expression.

Blood ◽

10.1182/blood.v110.11.4680.4680 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4680-4680

Author(s):

Farouk Meklat ◽

Yana Zhang ◽

Zhiqing Wang ◽

Jian Zhang ◽

Sukhrob Mustalov ◽

...

Keyword(s):

Vaccine Development ◽

Tumor Vaccine ◽

Early Stage ◽

Disease Stage ◽

Early Disease ◽

Early Stage Disease ◽

Stage Disease ◽

Ct Antigen ◽

Cancer Testis ◽

Protamine 1

Abstract Despite advances in modern chemotherapy, CLL remains incurable. CLL is an indolent disease. It expresses a panel of Cancer-Testis (CT) antigens. CLL leukemia cells are susceptible to the cytotoxicity of T cells. CLL is, therefore, an ideal disease for immunotherapeutic approaches. Immunotherapy, in addition to being less toxic and more specific than chemotherapy, provides a different mode of cytotoxicity that may synergize with that induced by chemotherapeutic agents. Immunotherapy also offers the prospect of inducing immune memory that may be important for long term disease-free survival of patients with CLL. However, there are obstacles that may prevent successful immunotherapy. CLL patients are generally immunosuppressed even before any therapy is given and the immunosuppression increases as the disease progresses. Therefore, any immunotherapeutic approaches for CLL should be aplied in early disease when immunosuppression is least encountered. We previously demonstrated the expression of a CT antigen, SEMG 1, in 3/9 patients with CLL. Furthermore, we also demonstrated that the presence of high titer IgG in the serum of patients expressing SEMG 1, suggesting the in vivo immunogenicity of SEMG 1 in the cancer-bearing autologous host. We have also recently used SEMG 1 as the bait in a yeast two-hybrid system of testicular cDNA library and identified that Protamine 1 is the interacting ligand of SEMG 1 and that Protamine 1 is also a novel CT antigen, suggesting that both SEMG 1 and Protamine 1 may be suitable antigens for tumor vaccine development. However, the expression of SEMG 1 and Protamine 1 in early CLL is unknown. We have in this study set out to determine whether or not SEMG 1 and/or Protamine 1 could be used for the design of tumor vaccine for the targeting of patients with early CLL, in particular, those with poor risk disease, as predicted by Zap 70 expression. Using pairs of sequence-specific primers in RT-PCR on a cohort of CLL (41 Stage 0/I and 6 Stage II/III), we found that SEMG 1 gene is expressed in 24/47 (51%) and Protamine 1 in 16/47 (34%) of CLL patients. Gene expression in most cases was associated with the detection by immunocytochemistry of SEMG 1 and/or Protamine 1 in the CLL cells. The expression frequency of SEMG1 and Protamine 1 in CLL did not appear to differ between early and late stage disease. 19/41 of patients with early stage disease and 5/6 of patients with late disease expressed SEMG 1; 12/41 of patients with early stage disease and 4/6 patients with late disease expressed Protamine 1. Furthermore, the expression of these antigens was equally distributed between Zap 70+ and Zap 70− CLL. SEMG 1 was expressed in 4/6 of Zap 70+ CLL (all 6 had early disease) and 2/9 of Zap 70− CLL (1/8 early disease and 1/1 late disease). Interestingly, although Protamine 1 expression in CLL predicted for SEMG 1 co-expression, only 67% of SEMG 1+ CLL expressed Protamine 1. Our results, therefore, suggest that both SEMG 1 and Protamine 1 are suitable targets for tumor vaccine development for some patients with early CLL, especially those with high risk disease, as predicted by Zap 70 expression.

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Preliminary phase II study results of capecitabine (X) + irinotecan (I) + bevacizumab (A) as first-line therapy for patients (pts) with metastatic colorectal cancer (MCRC)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14502 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14502-14502

Author(s):

S. Beslija ◽

M. Banjin ◽

S. Jungic ◽

N. Obralic ◽

G. Kecman-Malcic ◽

...

Keyword(s):

Adverse Events ◽

Phase Ii ◽

Response Rate ◽

Early Stage ◽

Progression Free Survival ◽

Disease Stage ◽

First Line ◽

Open Label ◽

First Line Therapy ◽

Study Results

14502 Background: The oral fluoropyrimidine X (Xeloda®) has improved efficacy, safety and convenience compared with 5-FU/LV in MCRC [Van Cutsem et al. Br J Cancer 2004] and early-stage colon cancer [Twelves et al. NEJM 2005]. A recent study showed that I + X q2w is active and well tolerated [Garcia-Alfonso et al. ESMO 2006]. The humanized monoclonal antibody A (Avastin®) targets VEGF and limits tumor angiogenesis. The addition of A to 5-FU/LV/I (IFL regimen) results in significant improvements in survival among pts with MCRC [Hurwitz et al. NEJM 2004]. Replacing 5-FU/LV with X in this combination is a logical step forward. Here we report data from an open-label phase II trial of XIA in MCRC. Methods: Pts with untreated, histologically confirmed MCRC received I 175 mg/m2 i.v. d1, X 1000 mg/m2 orally bid d2–8, and A 5 mg/m2 d1. Treatment was repeated q2w x12 cycles in the absence of disease progression or unacceptable toxicity. Pts without progressive disease after 12 cycles of XIA continued on the same dose of A + X 1500 mg/m2 bid d2–8, q2w. The primary endpoint was progression-free survival (PFS); secondary endpoints were response rate (RECIST), overall survival (OS), safety, and quality of life. Results: 24 out of a planned total of 32 pts have been enrolled. Baseline characteristics are: M/F 50%/50%; median age 53 years (range 30–70); disease stage at initial diagnosis IIIA/IIIB/IV 29%/21%/50%; no. of metastatic sites 1/>1 50%/50%; most common metastatic site liver; prior adjuvant therapy 33% (Mayo 5-FU/LV). Pts received a median of 12 cycles (range 1–18) of XIA. All 24 pts are evaluable for safety and 22 for efficacy. The overall response rate is 77% (4 CR, 13 PR); 2 pts (9%) have stable disease and 3 have progressed. One pt has died. Median PFS and median OS have not yet been reached. The only grade 3 adverse events are diarrhea (13%), fatigue (4%), mucositis (4%), enteritis (4%), ileus (4%); there is one report of grade 4 leucopenia. All other adverse events are mild-to-moderate. Conclusions: The XIA combination appears to be highly active and well tolerated as first-line treatment for MCRC, providing support for further evaluation of this combination. No significant financial relationships to disclose.

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Response to PD-1 inhibition in early- and late-relapsing cutaneous melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e21038 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e21038-e21038

Author(s):

Kelly Fitzgerald ◽

Adil Daud

Keyword(s):

Overall Response Rate ◽

Response Rate ◽

Early Stage ◽

Stage I ◽

Definitive Treatment ◽

Early Stage Disease ◽

Overall Response ◽

Stage Disease ◽

The Difference ◽

Time To Relapse

e21038 Background: Up to 45% of stage I-II melanomas will relapse within 5 years, and some relapses occur more than 10 years after surgical resection. Little is known about the differences in tumor characteristics, including immunogenicity, of early- vs. late-relapsing melanoma, or the implication of these differences in response to PD-1 inhibition. Methods: A retrospective cohort study was conducted to compare time from definitive treatment of localized melanoma to relapse with response to pembrolizumab. Patients with prior stage I-II melanoma who relapsed, and then treated with pembrolizumab, were included in the study. Time to relapse was compared with overall response rate. Results: Among the study population, 66 patients initially presented with early stage disease that relapsed within the study period. The median time to relapse was 5 years (range 0.5-33 years, interquartile range 7.25, Q1 = 2, Q2 = 9.25). 9 patients (14%) relapsed within 2 years of surgery; these patients had a higher overall response rate to pembrolizumab than late-relapsing patients with marginal significance (88% vs 50%, p = 0.056). The difference became less significant when patients who relapsed before or after 5 years (70% vs 47%, respectively, p = 0.20), and before or after 10 years (64% vs 45%, p = .31). Conclusions: Patients with early-relapsing melanoma had higher ORR to pembrolizumab than patients with late-relapsing disease, with early relapse defined as earlier than 2 years from definitive surgical intervention. Late relapsing tumors may harbor mechanisms of resistance to immune checkpoint inhibition.

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A Retrospective Analysis of Outcomes of Diffuse Large B Cell Lymphoma (DLBCL) in the Elder Patients in China

Blood ◽

10.1182/blood-2018-99-116641 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5410-5410

Author(s):

Peng Liu ◽

Ying Han ◽

Jianliang Yang ◽

Xiaohui He ◽

Changgong Zhang ◽

...

Keyword(s):

Cell Lymphoma ◽

Early Stage ◽

B Cell Lymphoma ◽

Disease Stage ◽

Early Stage Disease ◽

Large B Cell Lymphoma ◽

Elder Patients ◽

Stage Disease ◽

Ann Arbor ◽

Advanced Disease Stage

Abstract Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis compared to the younger population, since older age is associated with comorbidity and suboptimal performance status leading to intolerance of chemo-immunotherapy. The outcome of DLBCL in the older patients (> 60 years) was well described in clinical trials with reported 5-year overall survival (OS) of 50-80% (Coiffier et al., N Engl J Med 2002). Since this group is often precluded from clinical trials and population-based studies are limited, optimal treatment strategy for the old patients with DLBCL remains controversial. Here, we describe a Chinese real-world experience of management of elderly DLBCL patients treated at National Cancer Hospital, China. Methods: This is a single-center, retrospective analysis of consecutive DLBCL patients aged ≥60 who planned to receive chemotherapy +/- rituximab. The standard regimens included 3-4 cycles (early stage disease) or 6 cycles (advanced) of R-CHOP like regimens (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) followed by two rituximab doses in fit patients; R-miniCHOP for unfit and R-CE(etoposide)OP for frail elder patients. Patient data including baseline characteristics, histology, clinical parameters, and treatment outcomes were extracted from hospital medical records. The primary endpoint was progression-free survival (PFS); secondary endpoint was OS. Statistical analyses included descriptive statistics and Kaplan Meier estimates. Results: From June 2006 to December 2012, 349 patients aged ≥60 years were included, in which 204 patients were aged <70 years (Table 1). 326 patients received chemotherapy or chemo-immunotherapy with rituximab. Median follow up was 82 months. Five year PFS and OS of the elder patients were 45.8% and 51.9%, respectively. Significant difference was seen between patients < 70 years and those ≥70 years in terms of PFS (51.0% vs 38.6%, p=0.030) and OS (58.3% vs 42.8%, p=0.007) (Figure 1). Patients with early-stage disease (Ann Arbor StageⅠ/Ⅱ) had better 5-year PFS (60.1% vs 23.5%, p<0.001) and OS (65.3% vs 30.9%, p<0.001) than patients with advanced disease stage (Ann Arbor Stage III/IV) (Figure2). In addition, regimen including rituximab significantly improved the survival than chemotherapy alone (5-year PFS: 37.3% vs 64.0%, p<0.001; 5-year OS: 44.5% vs 69.3%, p<0.001), especially in patients ≥70 years, which almost doubled 5-year PFS and OS (5-year PFS: 25.4% vs 50.7%, p<0.001; 5-year OS: 28.8% vs 56.0%, p<0.001) (Figure3). Conclusions: Elder age (≥70 years) and advanced disease stage (Ann Arbor Stage III/IV) are associated with poor PFS and OS in Chinese elder DLBCL patients. The addition of rituximab significantly improves the survival compared to chemotherapy alone, especially in patients aged ≥70 years. These findings underscore the importance of personalized evaluation and treatment in elder patients with DLBCL. Disclosures No relevant conflicts of interest to declare.

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Recent advances in understanding and managing cutaneous T-cell lymphomas

F1000Research ◽

10.12688/f1000research.21922.1 ◽

2020 ◽

Vol 9 ◽

pp. 331

Author(s):

Patrick M. Brunner ◽

Constanze Jonak ◽

Robert Knobler

Keyword(s):

T Cell ◽

Early Stage ◽

Disease Stage ◽

Treatment Modalities ◽

Early Stage Disease ◽

T Cell Lymphomas ◽

Stage Disease ◽

Related Quality ◽

Health Related ◽

Stage Ivb

Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of extranodal non-Hodgkin lymphomas involving primarily the skin and mycosis fungoides is its most frequent entity. Whereas most patients show an indolent course in early disease (clinical stages IA to IIA), some patients progress to advanced disease (stage IIB or higher), and the 5-year survival rate is unfavorable: only 47% (stage IIB) to 18% (stage IVB). Except for allogeneic stem cell transplantation, there is currently no cure for CTCL and thus treatment approaches are palliative, focusing on patients’ health-related quality of life. Our aims were to review the current understanding of the pathogenesis of CTCL, such as the shift in overall immune skewing with progressive disease and the challenges of making a timely diagnosis in early-stage disease because of the lack of reliable positive markers for routine diagnostics, and to discuss established and potential treatment modalities such as immunotherapy and novel targeted therapeutics.

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Matching for 12 HLA Alleles Is Associated with a Significantly Superior Survival Due to a Lower Mortality in Recipients of Unrelated Donor Haematopoietic Cell Transplants for Early but Not Late Stage Leukaemia.

Blood ◽

10.1182/blood.v110.11.3056.3056 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3056-3056

Author(s):

B.E. Shaw ◽

N.P. Mayor ◽

A.-M. Little ◽

Nigel H. Russell ◽

A. Pagliuca ◽

...

Keyword(s):

Late Stage ◽

Early Stage ◽

Disease Stage ◽

Unrelated Donor ◽

Disease Relapse ◽

Early Stage Disease ◽

Hla Alleles ◽

Graft Versus Host ◽

Multiple Loci ◽

Stage Disease

Abstract Recipient/donor HLA matching is an important determinant of outcome in transplantation using volunteer unrelated donor (VUD). The degree of matching remains controversial. Some data suggest that disease stage is an important factor to consider when assessing the need for a well-matched donor. We analysed the impact of matching for 12 HLA alleles at six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) in a cohort of 458 patients receiving VUD transplants for leukaemia (142 CML, 170 AML, 146 ALL). Of the pairs, 84 were matched for 12/12 alleles, 250 and 124 were mismatched for one locus or more than one locus respectively (graft versus host vector). Most single locus mismatches were at DPB1 (218/250, 87%). In multiply mismatched pairs the loci were: DPB1 plus one other locus (81), 2 other loci excluding DPB1 (10) and more than 2 loci (33). Patients receiving 12/12 matched grafts had a significantly better survival than those who had mismatched grafts (7 years: 45% vs 30%, p=0.022) and those matched for 10/10 alleles (p=0.050). The outcome was not significantly different dependent on whether the mismatch was at single or multiple loci, nor whether the single mismatch was at DPB1 compared to any other HLA locus. Disease stage was a significant determinant of outcome, with patients transplanted in early stage disease (defined as CR1 or CP1, N=222) having a superior outcome to those with late stage disease (N=236) (7 year: 42% vs 28%; p=0.002) In patients with early stage disease, the survival was significantly better if 12/12 matched compared to the mismatched group (7 years: 62% vs 36%; p=0.005). Other factors associated with a significantly improved survival in this cohort were: patient age below the median (32 years), patient CMV seronegativity and CML (rather than acute leukaemia). In multivariate analysis, pairs matched for less than 12/12 HLA alleles (HR=1.8; CI 1.0–3.0; p=0.034) and acute leukaemia (HR=1.8; CI 1.2–2.6; p=0.003) had a significantly worse survival. The reason for the inferior outcome was a significantly worse transplant related mortality (TRM) in the mismatched pairs (p=0.006). This was 16%, 32% and 48% at 100 days, 1 and 7 years in the mismatched group, compared to 9%, 13% and 21% in the matched group. While the incidence of acute graft versus host disease (GvHD) overall was not increased in the mismatched group, the incidence of grade III/IV GvHD was higher (12/12 match = 0%, single locus mismatch = 2%, multiple loci=13%; p=0.002) and this was associated with a higher TRM (p=0.002). There was no significant impact of mismatching on chronic GvHD or disease relapse. Unlike these data, in the late disease stage cohort there was no effect of 12/12 matching status on survival (7 years: 25% vs 28%, NS) or TRM. However, there was an increase in GvHD in HLA mismatched pairs (acute, p=0.012; chronic, p=0.015) and the presence of cGvHD was protective against disease relapse (p=0.044). These data suggest that in patients transplanted at an early disease stage, matching for 12 HLA alleles is important to improve survival. In later stage disease the presence of an HLA mismatch may increase the incidence of GvHD and consequently of the graft versus leukaemia effect and hence be tolerated overall.

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Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study

Blood ◽

10.1182/blood-2011-12-396556 ◽

2012 ◽

Vol 119 (25) ◽

pp. 6005-6015 ◽

Cited By ~ 61

Author(s):

Stephen J. Proctor ◽

Jennifer Wilkinson ◽

Gail Jones ◽

Gillian C. Watson ◽

Helen H. Lucraft ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cox Regression ◽

Early Stage ◽

Univariate Analysis ◽

Central Element ◽

Disease Stage ◽

Advanced Stage ◽

Early Stage Disease ◽

Large Patient ◽

Stage Disease

Abstract The SHIELD program for Hodgkin lymphoma in patients 60 years of age or older, prospectively evaluated clinical features and outcome in a large patient cohort (n = 175). The central element was a phase 2 study of VEPEMB chemotherapy (n = 103, median age 73 years) incorporating comorbidity assessment. A total of 72 other patients were treated off-study but registered prospectively and treated concurrently with: ABVD (n = 35); CLVPP (n = 19), or other (n = 18). Of VEPEMB patients, 31 had early-stage disease (stage 1A/2A) and received VEPEMB 3 times plus radiotherapy. Median follow-up was 36 months. Complete remission (CR) rate (intention-to-treat) was 74% and 3-year overall survival (OS) and progression-free survival (PFS) were 81% and 74%, respectively. A total of 72 patients had advanced-stage disease (stage 1B/2B/3 or 4) and received VEPEMB 6 times. CR rate was 61% with 3-year OS and PFS of 66% and 58%, respectively. Of patients achieving CR, 13% with early-stage and 5% with advanced-stage disease progressed. Overall treatment-related mortality was 7%. In patients treated with curative intent with VEPEMB, ABVD, and CLVPP (n = 157), CR linked to several factors in univariate analysis. In a Cox regression model only, obtaining CR remained significant for OS and CR plus comorbidity and age for PFS. RS-EBV status had no significant effect on outcome.

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Molecular estimation of neurodegeneration pseudotime in older brains

Nature Communications ◽

10.1038/s41467-020-19622-y ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Sumit Mukherjee ◽

Laura Heath ◽

Christoph Preuss ◽

Suman Jayadev ◽

Gwenn A. Garden ◽

...

Keyword(s):

Late Stage ◽

Late Onset ◽

Early Stage ◽

Disease Onset ◽

Postmortem Brain ◽

Disease Stage ◽

Rna Seq ◽

Early Stage Disease ◽

Molecular Changes ◽

Stage Disease

AbstractThe temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage–or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10−5), Aβ (CERAD score, P = 1.8 × 10−5), and cognitive diagnosis (P = 3.5 × 10−7) of late-onset (LO) AD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.

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Survival Outcomes and Prognostic Factors in Mycosis Fungoides/Sézary Syndrome: Validation of the Revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer Staging Proposal

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.7665 ◽

2010 ◽

Vol 28 (31) ◽

pp. 4730-4739 ◽

Cited By ~ 407

Author(s):

Nita Sally Agar ◽

Emma Wedgeworth ◽

Siobhan Crichton ◽

Tracey J. Mitchell ◽

Michael Cox ◽

...

Keyword(s):

Prognostic Factors ◽

International Society ◽

Cell Transformation ◽

Early Stage ◽

Large Cell ◽

Early Stage Disease ◽

Stage Disease ◽

Cutaneous Lymphomas ◽

Large Cell Transformation ◽

Male Sex

Purpose We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal. Patients and Methods Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models. Results The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival. Conclusion This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.

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Clinical outcomes and impact of prognostic factors following adjuvant radiotherapy in oral tongue cancer patients

The Egyptian Journal of Otolaryngology ◽

10.1186/s43163-021-00168-9 ◽

2021 ◽

Vol 37 (1) ◽

Author(s):

Sidharth Pant ◽

Punita Lal ◽

Shagun Misra ◽

Piyush Gupta ◽

K. J. Maria Das ◽

...

Keyword(s):

Prognostic Factors ◽

Cancer Patients ◽

Advanced Disease ◽

Tongue Cancer ◽

Early Stage ◽

Locally Advanced ◽

Oral Tongue ◽

Early Stage Disease ◽

Stage Disease ◽

Oral Tongue Cancer

Abstract Background The purpose of the study was to evaluate survival outcomes in post-operative oral tongue cancer patients undergoing adjuvant radiotherapy (RT) at a tertiary cancer care center and to critically review the impact of various clinical-pathological factors on recurrence and survival. Demographic factors, stage of all the histology proven oral tongue cancer, and treatment details were documented. Overall survival (OS) and recurrence-free survival (RFS) were analyzed along with the potential prognostic factors affecting outcome. Results One hundred forty-four post-operative oral tongue cancer patients referred to our department for adjuvant treatment were evaluated. Median age at presentation was 45 years. Forty-seven patients had pathological early stage disease (stages I and II) and 95 had locally advanced (stages III and IV) disease while post-op details were not present in 2 patients. At a median follow-up of 87 months (60–124) of alive patients, the median RFS for entire cohort was 62 months while median OS was 74 months respectively. Age, perineural invasion (PNI), and grade of the tumor emerged as independent prognostic factors for OS and RFS. Among patients with early stage disease, depth of invasion (DOI), age, and PNI were found as independent prognostic factors for RFS and OS. In locally advanced disease, higher grade, age, and PNI independently impacted the respective survival end points. Conclusions Age (> 45 years), higher grade, and presence of PNI showed inferior survival outcomes across the sub-groups (early versus locally advanced disease). This may warrant adjuvant treatment intensification. DOI > 10 mm was particularly found to worsen survival in early node negative SCC oral tongue patients.

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