Outcome of Treatment with Fludarabine Versus Fludarabine and Cyclophosphamide in Chronic Lymphocytic Leukemia (CLL) Is Adversely Impacted by High Risk Genetic Features: Results from ECOG 2997.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3487-3487 ◽  
Author(s):  
Michael R. Grever ◽  
David M. Lucas ◽  
Gordon W. Dewald ◽  
Donna S. Neuberg ◽  
Ian W. Flinn ◽  
...  
Keyword(s):  
High Risk ◽  
P53 Mutation ◽  
Hazard Ratio ◽  
Phase Iii ◽  
P53 Mutations ◽  
Interphase Cytogenetics ◽  
Molecular Features ◽  
Mutational Status ◽  
Significant Difference ◽  
The Impact

Several prognostic factors including un-mutated VH mutational status, select interphase cytogenetic abnormalities [del(11q22.3), del(17p13.1)] and p53 mutations have been associated with shorter interval time from diagnosis to symptomatic disease requiring treatment, shortened progression-free survival (PFS) and overall survival (OS). Limited prospective data exists relative to the relevance of these biologic markers on PFS following treatment with modern therapies for CLL. E2997 is a randomized phase III trial of 278 previously untreated, symptomatic CLL patients who received fludarabine and cyclophosphamide (FC) versus fludarabine (F). We analyzed the response rates and PFS of the patients for whom interphase cytogenetics, VH mutational status, and p53 mutational status studies have been completed. FC therapy had a higher complete response (CR) (23% versus 5%, p<0.002), overall response [OR] (73% versus 50%, p<0.002), and median PFS (33.5 months versus 15 months, p<.0001) as compared to F. The CR and OR was not different based upon interphase cytogenetics or VH mutational status for the entire group of patients or when analyzed by arm of treatment. However, the OR for pts with del(17) or p53 mutations was lower in both the FC arm (69%, versus 76% in patients with normal p53) and F arm (27%, versus 54% in normal p53). Using the Dohner hierarchical classification [del(17p)>del(11q)>del(6q)>tri12>normal> del(13q14)], the relationship of interphase cytogenetics, VH mutational status and p53 mutational status with PFS is summarized below: Median PFS on FC (months) Median PFS on F (months) NR = median not reached; p53 mut+ = mutation present del(17p) 11.9 8.2 del(11q) 30.6 12.8 del(6q) 26.9 26.7 tri 12 NR 20.3 normal NR 11.2 del(13q) NR 21.2 del(17p)/p53 mut+ 11.9 8.9 no del(17p)/p53 mut+ NR 17.8 VH<98% NR 21.2 VH>98% 21.4 13.4 Using the interphase cytogenetic groups, there was a significant difference in PFS for both the FC (p=0.04) and F (p=0.01) treatment arms. Similarly, the presence of a p53 mutation or deletion [del(17p)] predicted for shorter PFS for both FC (p=0.005) and F (p=0.02) therapies. PFS did not statistically differ among VH mutational groups for either arm. We next investigated a Cox proportional hazards analysis to assess the impact of multiple molecular features and treatment arm on PFS. Treatment with F (hazard ratio 3.14, p<0.0001), presence of del(17p) or p53 mutation (hazard ratio 3.13, p=0.0001), and presence of del(11q) (hazard ratio 2.067, p=0.019) were highly significant in the model. Finally, VH unmutated status and del(11q) were highly associated. In conclusion, our data demonstrate that high risk genomic features including p53 mutations, del(17p), and del(11q) are highly predictive of shortened PFS. Our data provide support for a risk-stratified therapy approach for the treatment of CLL.

scholarly journals Structural Variants Involving MLLT10/AF10 Are Associated with Adverse Outcome in AML Regardless of the Partner Gene - a COG/Tpaml Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 461-461 ◽  
Author(s):  
Rhonda E. Ries ◽  
Amanda R. Leonti ◽  
Timothy Junius Triche ◽  
Robert B. Gerbing ◽  
Betsy A Hirsch ◽  
...  
Keyword(s):  
High Risk ◽  
Adverse Outcome ◽  
Adverse Outcomes ◽  
Fusion Partner ◽  
Structural Variants ◽  
Full Spectrum ◽  
Molecular Features ◽  
Mutational Status ◽  
Significant Difference ◽  
The Impact

The MLLT10 gene, a known fusion partner for KMT2A, encodes AF10 protein, a transcription factor that binds unmodified histone H3 and regulates DOT1L expression. KMT2A-MLLT10 fusion portends adverse outcome, but MLLT10 function and prognostic implications in partnership with other genes has not been defined. In comprehensive transcriptome and karyotype evaluation of 2226 children and young adults (0-30 years), we defined the full spectrum of MLLT10 fusions, identified new fusion partners, and correlated MLLT10 structural variants with clinical outcome. We also evaluated transcription and methylation profiles to identify genes dysregulated in MLLT10 fusions with and without KMT2A. 2226 patients treated on Children's Oncology Group (COG) trials AAML0531 and AAML1031 were evaluated by transcriptome profiling and/or karyotyping to identify leukemia associated fusions and copy number changes associated with prognosis. Collectively, 127 patients (5.7%) had primary fusions involving MLLT10: 104 (82%) involving KMT2A (KMT2A-MLLT10), and 23 patients (18%) revealed other fusion partners (MLLT10-X). Alternate, recurrent fusion partners included PICALM (n=13), DDX3X (n=2), and TEC (n=2), while fusions with 6 other partner genes (DDX3Y, CEP164, NAP1L1, SCN2B, TREH, and XPO1) were each identified in single patients. Given the known association of KMT2A-MLLT10 fusions with adverse outcome, we sought to determine whether MLLT10-X had distinct characteristics and comparable outcomes. Initial comparison of disease characteristics in patients with and without KMT2A as fusion partner showed significant differences in age at diagnosis. Those with KMT2A-MLLT10 had a median age of 1.7 years (range 0-21.3), compared to 12.7 years (range 1.4-18.9) in those with MLLT10-X (p ≤ 0.001). There was no significant difference in gender, race, mutational status, or white blood cell count between these two cohorts. MLLT10 rearranged patients (n=127) demonstrated adverse outcomes, with 5-year event-free survival (EFS) of 18.6% vs. 49% in non-MLLT10 rearranged patients (N=1953, p&lt;0.001, Fig 1A) and poorer 5 year overall survival (OS, 38.8% vs. 65.4%, p ≤ 0.001). Next, we investigated the outcome of MLLT10 rearranged patients with and without KMT2A as a fusion partner. Patients with KMT2A-MLLT10 fusions had an EFS from study entry of 19.5% vs. 12.7% for those with alternate fusion partners (p=0.628, Fig 1B). The two cohorts also had similar relapse risk (RR) from remission with 84.7% (KMT2A-MLLT10) to that of 74.6% for MLLT10-X (p=0.876). Next we explored the transcriptome profile of patients with MLLT10 fusions to determine the impact of fusion partners, using ribodepleted RNA-seq data from 1049 patients treated on COG AAML1031. MLLT10-fusion-positive cases (n=66) were compared to other AML cases (n=983) in a differential expression (DE) analysis (limma/voom) (Fig 1C). Of 1,910 genes significantly differentially expressed, HOXA family genes were among the top 30 upregulated genes, with HOXA11 identified as &gt;6 logFC, or over 400x higher on average in MLLT10 rearranged patients. To determine if patients with MLLT10 fusions had distinct epigenetic profiles, we performed differential methylation analyses on samples from normal bone marrow and patients with 4 high-risk molecular features: MLLT10 rearranged, KMT2A rearranged, NUP98-NSD1 fused, and FLT3-ITD, across nearly 1 million CpG sites on the Infinium EPIC array (Illumina, CA). After fitting a multivariate model with all of the interacting molecular features, the 250 most discriminative regions were extracted and plotted (ComplexHeatmap) (Fig 1D). Strikingly, patients with MLLT10-X fusions cluster discretely with ultra-high-risk NUP98-NSD1 fusion patients, showing a broadly hypermethylated profile, while KMT2A-MLLT10 patients cluster within the larger KMT2A category and show far fewer hypermethylated regions. We identified patients with MLLT10 fusion partners not previously described, and compared them to other AML patients, as well as patients with known MLLT10 partners KMT2A and PICALM. All MLLT10-aberrant cases had poor EFS and OS, high RR, overexpressed HOXA genes, and distinct DNA methylation profiles, while patients with MLLT10-X fusions tend to be older children. Regardless of fusion partner, patients with MLLT10 fusions exhibit very high risk, and should be prioritized for alternative therapeutic intervention. Disclosures Farrar: Novartis: Research Funding. Deshpande:A2A Pharmaceuticals: Consultancy; Salgomed Therapeutics: Consultancy.

A novel interaction of genotype, gender, and adjuvant treatment in survival after resection of stage III colon cancer: Results of CALGB 89803.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 452-452
Author(s):  
Chloe Evelyn Atreya ◽  
Robert S. Warren ◽  
Donna Niedzwiecki ◽  
Robert J. Mayer ◽  
Richard M. Goldberg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Phase Iii ◽  
Zinc Binding ◽  
Stage Iii ◽  
P53 Mutations ◽  
Stage Iii Colon Cancer ◽  
Mutational Status ◽  
The Impact

452 Background: The p53 tumor suppressor gene is frequently mutated in colorectal cancer, but reports on the effect of p53 mutations on response to adjuvant chemotherapy and survival are inconclusive. This study investigates whether p53 mutational status (wild-type, zinc or non-zinc binding mutations) impacts survival following adjuvant therapy containing fluorouracil/leucovorin with or without irinotecan (5FU/LV or IFL) in women and men with stage III colon cancer. Methods: As part of a retrospective analysis of prospectively accrued data, p53 mutational status was determined for 609 patients with stage III colon cancer who were randomized on CALGB 89803, a phase III adjuvant chemotherapy trial. p53 exons 5-8 were analyzed by direct sequencing or sequencing by hybridization. p53 mutations were identified in 276 tumors (45%), of which 134 were in the zinc binding and 142 were in the non-zinc binding regions of the core domain. Cox regression was used to study the impact of p53 mutational status, sex, and adjuvant chemotherapy on disease-free (DFS) and overall survival (OS). Results: p53 mutational status did not predict differential survival or response to adjuvant therapy among the 609 patients assessed. However, a significant sex by treatment interaction was observed for both DFS (Pinteraction=0.008) and OS (Pinteraction=0.002). Significant differences in DFS by p53 mutational status were observed among women (logrank P = 0.009). No such differences were observed among men (logrank P = 0.33). Similar results were observed for OS. There was marginal evidence of a treatment-related impact on the interaction between sex and p53 mutational status for both DFS and OS (DFS Pinteraction = 0.07; OS Pinteraction = 0.11). There was a trend toward improved OS when women with zinc binding mutations received IFL versus 5FU/LV (P = 0.08) and toward worse DFS when women with non-zinc binding mutations were treated with IFL versus 5FU/LV (P =0.08). Conclusions: This exploratory subset analysis suggests that p53 mutational status may be used to predict prognosis in a sex- and potentially chemotherapeutic regimen-specific manner.

Select High Risk Genetic Features Predict Earlier Progression Following Chemoimmunotherapy with Fludarabine and Rituximab in Chronic Lymphocytic Leukemia (CLL): Preliminary Justification for Risk-Adapted Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 476-476 ◽  
Author(s):  
John C. Byrd ◽  
John G. Gribben ◽  
Bercedis Peterson ◽  
Michael R. Grever ◽  
Gerard Lozanski ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Hierarchical Classification ◽  
P53 Mutation ◽  
Low Risk ◽  
P Value ◽  
P53 Mutations ◽  
Cytogenetic Abnormalities ◽  
Mutational Status ◽  
Risk Patients

Abstract Several prognostic factors in CLL including un-mutated VH mutational status, select interphase cytogenetic abnormalities [del(11q22.3), del(17p13.1)], and p53 mutations have been associated with decreased time from diagnosis to symptomatic disease requiring treatment as well as shortened progression-free survival (PFS) and overall survival (OS). To date, the impacts of these prognostic factors on treatment outcome with fludarabine and rituximab combination treatments have not been explored. The Cancer and Leukemia Group B recently reported results of a randomized phase II study (CALGB 9712) that added rituximab concurrently or sequentially to fludarabine as initial therapy for symptomatic, untreated CLL (Blood2003; 101:6). After a recently updated median follow-up of 43 months, PFS and OS are still similar in both arms. Of the 104 patients enrolled, we studied 88 patients for whom pre-treatment samples were available to examine the impact of VH mutational status (≥97% defined as un-mutated), common cytogenetic abnormalities, and p53 mutational status on outcome relative to CR (complete remission) and PFS. OS was not examined because only 13 deaths have occurred to date. A total of 46 out of 75 (61%) patients were VH un-mutated CLL. Fifteen (52%) of 29 mutated and 20 (43%) of 46 un-mutated patients achieved a CR (p= 0.49). The median PFS among the VH mutated patients was 46 months [95% CI (40, 54)] whereas for un-mutated it was 32 months [95% CI (22, 42)] (p= 0.05). Controlling for differences in age, sex, WBC, LDH, and stage resulted in an adjusted p-value of p=0.03. Only four patients had p53 mutations, preventing analysis of this biologic feature independently. Using the Dohner hierarchical classification, the frequency CR rate and PFS for each group are summarized below. Cytogenetic Abnormality: del(17p) del(11q) del(6q) tris 12 del(13q) Normal No. (%) pts 3 (3%) 15 (17%) 1 (1%) 23 (26%) 24 (27%) 22 (25%) CR (%) 0 53 100 25 38 64 PFS (months) 18 25 42 42 45 49 Using the hierarchical classification of Dohner, there was not a difference in CR rate (p=0.25) and PFS (p=0.10). Controlling for differences in age, sex, WBC, LDH, and stage resulted in an adjusted p-value of p=0.04. The PFS for the del(17p13.1) and del(11q22.3) patients was significantly shorter than that observed for the remaining cytogenetic groups (p=0.03). We next sought to define a high-risk group of CLL patients, as having any of the following: VH un-mutated (≥97%), del(17p), del (11q), or non-silent p53 mutation. Using this classification, 35 patients were assigned to the low-risk and 53 to the high-risk groups. The CR rate in each group was 43%. However, the median PFS among the low risk patients was 45 months with 95% CI (45, NA) whereas the median PFS among the high-risk patients was 32 months with 95% CI (22, 42) (p=0.004). These data demonstrate that high risk CLL patients characterized by VH un-mutated (≥97%), del(17p), del (11q), or non-silent p53 mutation appear to have a shorter PFS with chemoimmunotherapy and define a subset of patients for whom additional novel treatment approaches should be targeted.

Select High-Risk Genetic Features Predict Earlier Progression Following Chemoimmunotherapy With Fludarabine and Rituximab in Chronic Lymphocytic Leukemia: Justification for Risk-Adapted Therapy

2006 ◽  
Vol 24 (3) ◽  
pp. 437-443 ◽  
Author(s):  
John C. Byrd ◽  
John G. Gribben ◽  
Bercedis L. Peterson ◽  
Michael R. Grever ◽  
Gerard Lozanski ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Prognostic Factors ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Interphase Cytogenetics ◽  
Mutational Status ◽  
The Impact

Purpose Several new prognostic factors predicting rapid disease progression in chronic lymphocytic leukemia (CLL) have been identified, including unmutated Ig VH mutational status, del(11)(q23), del(17)(p13.1), and p53 mutations. To date, the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy. Methods We examined the impact of these new prognostic factors on predicting treatment outcome in symptomatic, untreated CLL patients who received chemoimmunotherapy with fludarabine and rituximab as part of a completed, randomized phase II study, Cancer and Leukemia Group B (CALGB) 9712. Results Eighty-eight patients treated as part of CALGB 9712 had detailed prognostic factor assessment performed. Using Ig VH mutational status to classify risk, there was no association between complete response rate with either unmutated Ig VH mutational status or high-risk interphase cytogenetics. However, the median progression-free survival (PFS; P = .048) and overall survival (OS; P = .01) were shorter among the Ig VH unmutated patients as compared with the Ig VH mutated patients. Using the hierarchical classification of Döhner, PFS (P = .005) and OS (P = .004) were significantly longer as the classification moved from high risk [del (11)(q22.3) or del (17)(p13.1)] to low risk. Conclusion These data demonstrate that high-risk CLL patients characterized by Ig VH unmutated (≥ 98%) or high-risk interphase cytogenetics, including either del(17p) or del(11q), appear to have a shorter PFS and OS with chemoimmunotherapy. Larger prospective studies will be required to determine the independent influence of Ig VH mutational status and interphase cytogenetics on treatment outcome.

Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997

2007 ◽  
Vol 25 (7) ◽  
pp. 799-804 ◽  
Author(s):  
Michael R. Grever ◽  
David M. Lucas ◽  
Gordon W. Dewald ◽  
Donna S. Neuberg ◽  
John C. Reed ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Significance ◽  
Variable Region ◽  
Hazard Ratio ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Therapeutic Trial ◽  
Cd38 Expression ◽  
Molecular Features ◽  
Mutational Status

Purpose Genomic features including unmutated immunoglobulin variable region heavy chain (IgVH) genes, del(11q22.3), del(17p13.1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome. Patients and Methods We prospectively evaluated the prognostic significance of a comprehensive panel of laboratory factors on both response and progression-free survival (PFS) using samples and data from 235 patients enrolled onto a therapeutic trial. Patients received either fludarabine (FL; n = 113) or fludarabine plus cyclophosphamide (FC; n = 122) as part of a US Intergroup randomized trial for previously untreated CLL patients. Results Complete response (CR) rates were 24.6% for patients receiving FC and 5.3% for patients receiving FL (P = .00004). PFS was statistically significantly longer in patients receiving FC (median, 33.5 months for patients receiving FC and 19.9 months for patients receiving FL; P < .0001). The occurrence of del(17p13.1) (hazard ratio, 3.428; P = .0002) or del(11q22.3) (hazard ratio, 1.904; P = .006) was associated with reduced PFS. CR and overall response rates were not significantly different based on cytogenetics, IgVH mutational status, CD38 expression, or p53 mutational status. Expression of ZAP-70, Bcl-2, Bax, Mcl-1, XIAP, Caspase-3, and Traf-1 was not associated with either clinical response or PFS. Conclusion These results support the use of interphase cytogenetic analysis, but not IgVH, CD38 expression, or ZAP-70 status, to predict outcome of FL-based chemotherapy. Patients with high-risk cytogenetic features should be considered for alternative therapies.

Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 500-500 ◽  
Author(s):  
Nadia Harbeck ◽  
Seock-Ah Im ◽  
Carlos H. Barrios ◽  
Herve R. Bonnefoi ◽  
Julie Gralow ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Hazard Ratio ◽  
Phase Iii ◽  
High Risk Population ◽  
Her2 Positive ◽  
Primary Endpoints ◽  
Significant Difference ◽  
Patient Reported

500 Background: The standard of care for HER2-positive EBC is chemotherapy plus one year of HER2-directed therapy. However, recurrence—particularly in high-risk populations—remains a problem, as does systemic chemotherapy-associated toxicity. In KAITLIN, we aimed to improve efficacy and reduce toxicity by replacing taxanes and trastuzumab with T-DM1. Methods: KAITLIN (NCT01966471) is a phase 3, randomized, open-label study that enrolled 1846 patients with adequately excised, centrally confirmed HER2-positive EBC either node-positive (LN+); or node-negative, HR-negative, and tumor size > 2.0 cm. Within 9 weeks of surgery, patients were randomized 1:1 to 3-4 cycles of anthracycline-based chemotherapy followed by 18 cycles of T-DM1 3.6 mg/kg + pertuzumab 420 mg q3w (loading dose [LD] 840 mg) (AC-KP) or taxane (3-4 cycles) + concurrent trastuzumab 6 mg/kg (LD 8 mg/kg) + pertuzumab 420 mg q3w (LD 840 mg) (AC-THP). Patients were stratified by world region, nodal status, HR status, and anthracycline type. Adjuvant radiotherapy and/or endocrine therapy was administered after 4 cycles of HER2-targeted therapy when indicated. The co-primary endpoints were invasive disease-free survival (IDFS) in the LN+ and in the ITT populations applying a hierarchical testing procedure. Secondary endpoints included overall survival (OS), patient-reported outcomes (PROs), and safety. Results: KAITLIN did not meet its co-primary endpoints. In LN+ patients (n = 1658), there was no significant difference between arms in IDFS event risk (stratified hazard ratio = 0.97; 95%CI 0.71–1.32). Three-year IDFS was 94.1% with AC-THP and 92.7% with AC-KP. Results were similar in the ITT population (stratified hazard ratio = 0.98; 95%CI 0.72–1.32; 3-year IDFS: 94.2% vs 93.1%). OS data are immature with an event rate of ~4%–5% in each arm. During the study overall, there was a similar incidence of grade ≥3 AEs (55.4% vs 51.8%) and SAEs (23.3% vs 21.4%) with AC-THP and AC-KP, respectively. More patients receiving AC-KP than AC-THP discontinued T-DM1 or trastuzumab, respectively, because of AEs (26.8% vs 4.0%). PRO data will be presented. Conclusions: Replacing adjuvant taxane and trastuzumab with T-DM1 did not result in significantly improved efficacy or overall safety. Nonetheless, in this high-risk population, a favorable IDFS outcome was achieved in both study arms. HP + chemotherapy remains the standard of care for patients with high-risk HER2-positive EBC. Clinical trial information: NCT01966471 .

scholarly journals Impact of pretreatment anemia on upfront abiraterone acetate therapy for metastatic hormone-sensitive prostate cancer: a multicenter retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Teppei Okamoto ◽  
Daisuke Noro ◽  
Shingo Hatakeyama ◽  
Shintaro Narita ◽  
Koji Mitsuzuka ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Abiraterone Acetate ◽  
Tumor Burden ◽  
Hazard Ratio ◽  
Historical Cohort ◽  
High Tumor Burden ◽  
Significant Difference ◽  
Hormone Sensitive ◽  
The Impact

Abstract Background Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. Methods We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). Results We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia. Conclusion Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

scholarly journals The impact of SARS-CoV-2 transmission fear and COVID-19 pandemic on the mental health of patients with primary immunodeficiency disorders, severe asthma, and other high-risk groups (Preprint)

2020 ◽  
Author(s):  
Fatih Çölkesen ◽  
Oguzhan Kilincel ◽  
Mehmet Sozen ◽  
Eray Yıldız ◽  
Sengul Beyaz ◽  
...  
Keyword(s):  
Mental Health ◽  
High Risk ◽  
Severe Asthma ◽  
Primary Immunodeficiency ◽  
Healthcare Workers ◽  
Depression Scale ◽  
High Risk Group ◽  
Primary Immunodeficiency Disorder ◽  
Significant Difference ◽  
The Impact

BACKGROUND The adverse effects of COVID-19 pandemic on the mental health of high-risk group patients for morbidity and mortality and its impact on public health in the long term have not been clearly determined. OBJECTIVE To determine the level of COVID-19 related transmission fear and anxiety in healthcare workers and patients with primary immunodeficiency disorder (PID), severe asthma, and the ones with other comorbidities. METHODS The healthcare workers and patients with PID, severe asthma (all patients receiving biological agent treatment), malignancy, cardiovascular disease, hypertension (90% of patients receiving ACEI or ARB therapy), diabetes mellitus (42 % of patients receiving DPP-4 inhibitor therapy) were included in the study. A total of 560 participants, 80 individuals in each group, were provided. The hospital anxiety and depression scale ( HADS ) and Fear of illness and virus evaluation (FIVE ) scales were applied to the groups with face to face interview methods. RESULTS The mean age was 49.30 years and 306 (55 %) were female. The FIVE Scale and HADS-A scale scores of health care workers were significantly higher than other groups' scores (p = 0.001 and 0.006). The second-highest scores belonged to patients with PID. There was no significant difference between the groups for the HADS-D score (p=0.07). The lowest score in all scales was observed in patients with hypertension. CONCLUSIONS This study demonstrated that in the pandemic process, patients with primary immunodeficiency, asthma patients, and other comorbid patients, especially healthcare workers, should be referred to the centers for the detection and treatment of mental health conditions.

scholarly journals Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy

2019 ◽  
Vol 17 (12) ◽  
pp. 1497-1504
Author(s):  
Lucas K. Vitzthum ◽  
Chris Straka ◽  
Reith R. Sarkar ◽  
Rana McKay ◽  
J. Michael Randall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
High Risk ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Short Term ◽  
Combined Androgen Blockade ◽  
Significant Difference ◽  
Androgen Blockade

Background: The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy. Methods: This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer–specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested. Results: The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85–1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93–1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57–0.95) and OS (SHR, 0.82; 95% CI, 0.73–0.93). Conclusions: In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.

scholarly journals Phase III Intergroup Trial of Adjuvant Androgen Deprivation With or Without Mitoxantrone Plus Prednisone in Patients With High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921

2018 ◽  
Vol 36 (15) ◽  
pp. 1498-1504 ◽  
Author(s):  
Maha Hussain ◽  
Catherine M. Tangen ◽  
Ian M. Thompson ◽  
Gregory P. Swanson ◽  
David P. Wood ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Adjuvant Radiation ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

Purpose Patients with high-risk prostate cancer after radical prostatectomy are at risk for death. Adjuvant androgen-deprivation therapy (ADT) may reduce this risk. We hypothesized that the addition of mitoxantrone and prednisone (MP) to adjuvant ADT could reduce mortality compared with adjuvant ADT alone. Methods Eligible patients had cT1-3N0 prostate cancer with one or more high-risk factors after radical prostatectomy (Gleason score [GS] ≥ 8; pT3b, pT4, or pN+ disease; GS 7 and positive margins; or preoperative prostate-specific antigen [PSA] > 15 ng/mL, biopsy GS score > 7, or PSA > 10 ng/mL plus biopsy GS > 6. Patients with PSA ≤ 0.2 ng/mL after radical prostatectomy were stratified by pT/N stage, GS, and adjuvant radiation plan and randomly assigned to ADT (bicalutamide and goserelin for 2 years) or ADT plus six cycles of MP. The primary end point was overall survival (OS). Median OS was projected to be 10 years in the ADT arm, requiring 680 patients per arm to detect a hazard ratio of 1.30 with 92% power and one-sided α = .05. Results Nine hundred sixty-one eligible intent-to-treat patients were randomly assigned to ADT or ADT + MP from October 1999 to January 2007, when the Data Safety Monitoring Committee recommended stopping accrual as a result of higher leukemia incidence with ADT + MP. Median follow-up was 11.2 years. The 10-year OS estimates were 87% with ADT (expected 50%) and 86% with ADT + MP (hazard ratio, 1.06; 95% CI, 0.79 to 1.43). The 10-year estimate for disease-free survival was 72% for both arms. Prostate cancer was the cause of death in 18% of patients in the ADT arm and 22% in the ADT + MP arm. More patients in the MP arm died of other cancers (36% v 18% in ADT alone arm). Conclusion MP did not improve OS and increased deaths from other malignancies. The DFS and 10-year OS in these patients treated with 2 years of ADT were encouraging compared with historical estimates, although a definitive conclusion regarding value of ADT may not be made without a nontreatment control arm.

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