scholarly journals Genomic Classifier Identifies Men With Adverse Pathology After Radical Prostatectomy Who Benefit From Adjuvant Radiation Therapy

2015 ◽  
Vol 33 (8) ◽  
pp. 944-951 ◽  
Author(s):  
Robert B. Den ◽  
Kasra Yousefi ◽  
Edouard J. Trabulsi ◽  
Firas Abdollah ◽  
Voleak Choeurng ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Optimal Timing ◽  
Adjuvant Radiation ◽  
Cox Regression Analysis ◽  
Pathologic Features

Purpose The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making. Patients and Methods GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic between 1990 and 2009. The primary end point was clinical metastasis. Prognostic accuracy of the models was tested using the concordance index for censored data and decision curve analysis. Cox regression analysis tested the relationship between GC and metastasis. Results The cumulative incidence of metastasis at 5 years after RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (P = .002). In multivariable analysis, GC and pre-RP prostate-specific antigen were independent predictors of metastasis (both P < .01). Within the low GC score (< 0.4), there were no differences in the cumulative incidence of metastasis comparing patients who received adjuvant or salvage RT (P = .79). However, for patients with higher GC scores (≥ 0.4), cumulative incidence of metastasis at 5 years was 6% for patients treated with adjuvant RT compared with 23% for patients treated with salvage RT (P < .01). Conclusion In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low GC scores are best treated with salvage RT, whereas those with high GC scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-RP RT.

A genomic classifier to identify men with adverse pathology post radical prostatectomy who benefit from adjuvant radiation therapy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 168-168
Author(s):  
Robert Benjamin Den ◽  
Kasra Yousefi ◽  
Edouard John Trabulsi ◽  
Firas Abdollah ◽  
Voleak Choeurng ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Multivariable Analysis ◽  
Optimal Timing ◽  
Adjuvant Radiation ◽  
Prognostic Accuracy ◽  
Pathologic Features ◽  
The Relationship

168 Background: The optimal timing of postoperative radiotherapy following radical prostatectomy (post-RP RT) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision-making. Methods: GC scores were calculated from 188 patients with pT3 or margin positive PCa, who received post-RP RT at Thomas Jefferson University and Mayo Clinic, between 1990 and 2009. The primary endpoint was clinical metastasis. Prognostic accuracy of the models were tested using c-index and decision curve analysis. Cox regression tested the relationship between GC and metastasis. Results: The cumulative incidence of metastasis at 5 years post-RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (p=0.002). In multivariable analysis, GC and pre-RP PSA were independent predictors of metastasis (both p<0.01). Within the low GC score (<0.4), there were no differences in the cumulative incidence of metastasis comparing those who received adjuvant or salvage RT (p=0.79). However, for patients with higher GC scores (≥0.4) cumulative incidence of metastasis at 5-year was 6% vs. 23% for patients treated with adjuvant vs. salvage RT (p<0.01). Conclusions: In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical/pathologic features. Though preliminary, patients with low GC are best treated with salvage radiation, while those with high GC benefit from adjuvant therapy. These findings provide the first rationale selection of timing of post-RP RT.

scholarly journals Predictive Factors and Oncologic Outcome of Downgrade to Pathologic Gleason Score 6–7 after Radical Prostatectomy in Patients with Biopsy Gleason Score 8–10

2019 ◽  
Vol 8 (4) ◽  
pp. 438 ◽  
Author(s):  
Doo Chung ◽  
Jong Lee ◽  
Hyeok Goh ◽  
Dong Koh ◽  
Min Kim ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Predictive Factors ◽  
Cox Regression ◽  
Specific Antigen ◽  
Surgical Margin ◽  
Positive Surgical Margin ◽  
Cox Regression Analysis ◽  
Pathologic Features

Gleason score (GS) 8–10 is associated with adverse outcomes in prostate cancer (PCa). However, biopsy GS (bGS) may be upgraded or downgraded post-radical prostatectomy (RP). We aimed to investigate predictive factors and oncologic outcomes of downgrade to pathologic GS (pGS) 6–7 after RP in PCa patients with bGSs 8–10. We retrospectively reviewed clinical data of patients with bGS ≥ 8 undergoing RP. pGS downgrade was defined as a pGS ≤ 7 from bGS ≥ 8 post-RP. Univariate and multivariate cox regression analysis, logistic regression analysis, and Kaplan–Meier curves were used to analyze pGS downgrade and biochemical recurrence (BCR). Of 860 patients, 623 and 237 had bGS 8 and bGS ≥ 9, respectively. Post-RP, 332 patients were downgraded to pGS ≤ 7; of these, 284 and 48 had bGS 8 and bGS ≥ 9, respectively. Prostate-specific antigen (PSA) levels; clinical stage; and adverse pathologic features such as extracapsular extension, seminal vesicle invasion and positive surgical margin were significantly different between patients with pGS ≤ 7 and pGS ≥ 8. Furthermore, bGS 8 (odds ratio (OR): 0.349, p < 0.001), PSA level < 10 ng/mL (OR: 0.634, p = 0.004), and ≤cT3a (OR: 0.400, p < 0.001) were identified as significant predictors of pGS downgrade. pGS downgrade was a significant positive predictor of BCR following RP in patients with high bGS (vs. pGS 8, hazard radio (HR): 1.699, p < 0.001; vs. pGS ≥ 9, HR: 1.765, p < 0.001). In addition, the 5-year BCR-free survival rate in patients with pGS downgrade significantly differed from that in patients with bGS 8 and ≥ 9 (52.9% vs. 40.7%, p < 0.001). Among patients with bGS ≥ 8, those with bGS 8, PSA level < 10 ng/mL, and ≤cT3a may achieve pGS downgrade after RP. These patients may have fewer adverse pathologic features and show a favorable prognosis; thus we suggest that active treatment is needed in these patients. In addition, patients with high-grade bGS should be managed aggressively, even if they show pGS downgrade.

scholarly journals Outcomes After Surgery and Radiotherapy for Spinal Myxopapillary Ependymoma

Neurosurgery ◽  
2014 ◽  
Vol 75 (3) ◽  
pp. 205-214 ◽  
Author(s):  
Chiaojung Jillian Tsai ◽  
Yucai Wang ◽  
Pamela K. Allen ◽  
Anita Mahajan ◽  
Ian E. McCutcheon ◽  
...  
Keyword(s):  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Gross Total Resection ◽  
Entire Group ◽  
Subtotal Resection ◽  
Myxopapillary Ependymoma ◽  
Adjuvant Radiation ◽  
Total Resection ◽  
Cox Regression Analysis

Abstract BACKGROUND: The role of radiotherapy after surgery for myxopapillary ependymoma (MPE) is unclear. OBJECTIVE: To review long-term outcomes after surgery, with or without radiation, for spinal MPE. METHODS: Fifty-one patients with spinal MPE treated from 1968 to 2007 were included. Associations between clinical variables and overall survival (OS), progression-free survival (PFS), and local control (LC) were tested with Cox regression analysis. RESULTS: The median age at diagnosis was 35 years (range, 8-63 years). Twenty patients (39%) had surgery alone, 30 (59%) had surgery plus radiotherapy (RT), and 1 (2%) had RT only. At a median follow-up of 11 years (range, 0.2-37 years), 10-year OS, PFS, and LC for the entire group were 93%, 63%, and 67%, respectively. Nineteen patients (37%) had disease recurrence, and the recurrence was mostly local (79%). Twenty-eight of 50 patients who had surgery (56%) had gross total resection; 10-year LC was 56% after surgery vs 92% after surgery and RT (log-rank P = .14); the median time of LC was 10.5 years for patients receiving gross total resection plus RT, and 4.75 years for gross total resection only (P = .03). Among 16 patients with subtotal resection and follow-up data, 10-year LC was 0% after surgery vs 65% for surgery plus RT (log-rank P = .008). On multivariate analyses adjusting for resection type, age older that 35 years at diagnosis and receipt of adjuvant radiation were associated with improved PFS (hazard ratio [HR]: 0.14, P = .003 and HR: 0.45, P = .009) and LC (HR: 0.22, P = .02 and HR: 0.45, P = .009). CONCLUSION: Postoperative radiotherapy after resection of MPE was associated with improved PFS and LC.

scholarly journals Gαs Protein Expression Is an Independent Predictor of Recurrence in Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lijuan Wang ◽  
Guihua Jin ◽  
Chenchen He ◽  
Xijing Guo ◽  
Xia Zhou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
G Protein ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Independent Predictor ◽  
Specific Antigen ◽  
Cox Regression Analysis ◽  
Pathologic Features ◽  
Psa Progression

Background. T393C polymorphism in the gene GNAS1, which encodes the G-protein alpha s subunit (Gαs) of heterotrimeric G protein, is significantly associated with the clinical outcome of patients suffering from several cancers. However, studies on the role and protein expression of Gαs subunit in prostate cancer were still unavailable.Methods. The immunohistochemical staining was used to assess Gαs expression through tissue microarray procedure of 56 metastatic PCas, 291 localized PCas, and 67 benign hyperplasia (BPH). Gαs expression was semiquantitatively scored and evaluated the correlation with pathologic parameters and biochemical recurrence of prostate-specific antigen (PSA).Results. Gαs expression was localized in nuclear and cytoplasm in prostate cancer cells and downregulated in metastatic PCa compared to localized PCa and BPH(P<0.001). Gαs was inversely associated with PSA level and Gleason scores; patients with low expression of Gαs had adverse clincopathological features. In multivariable Cox regression analysis, high Gαs expression and Gleason scores were independent predictors of both PSA progression-free and overall survival.Conclusions. Gαs down-expression is associated with adverse pathologic features and clinical PSA biochemical recurrence of prostate cancer. Gαs is an independent predictor to help determine the risk of PSA progression and death.

Validation of a genomic classifier for predicting biochemical failure following postoperative radiation therapy in high-risk prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 10-10
Author(s):  
Robert Benjamin Den ◽  
Felix Yi-Chung Feng ◽  
Timothy Norman Showalter ◽  
Mark Vikas Mishra ◽  
Edouard John Trabulsi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Background Radiation ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Biochemical Failure ◽  
Receiver Operating Curve ◽  
Gleason Grade ◽  
Tumor Focus

10 Background: Radiation therapy (RT) is commonly offered in the post radical prostatectomy (RP) setting, however response varies. We hypothesized that the genomic classifier ([GC] Decipher) score would predict biochemical failure (BF) and distant metastasis (DM) in men receiving post−RP RT. Methods: Under an institutional review board approved protocol, 223 men who underwent post−RP RT at the Kimmel Cancer Center of Thomas Jefferson University for pT3 or margin positive disease from 1990 to 2009 were identified. RNA was extracted from 143 patients with paraffin−embedded specimens and expression quantified from the highest Gleason grade tumor focus using a high−density oligonucleotide microarray. Excluding men who received neo−adjuvant therapy, 139 patients remained for GC calculation. Area under the receiver operating curve (AUC), decision curves, cumulative incidence accounting for competing risks, and multivariable Cox regression analyses were used to assess GC for predicting BF and DM after RT in comparison to nomograms. Results: The AUC of CAPRA-S was 0.67 (95% CI 0.58−0.77) and 0.65 (95% CI 0.44−0.86) for BF and DM, respectively. Integration of GC improved AUC to 0.75 (95% CI 0.66−0.84) and 0.77 (95% CI 0.64−0.91) for BF and DM, respectively. Cumulative incidence of BF at 8 years post-RT was 21%, 48%, and 81% for low (less than 0.4), intermediate (0.4 to 0.6), and high (more than 0.6) GC, respectively (p<0.00001). In multivariable analysis, patients who received RT early (pre−RT prostate-specific antigen [PSA] less than 1 ng/mL) had a BF benefit with a significantly reduced hazard ratio (HR) of 0.32 (95% CI 0.11−0.96, p<0.042). Patients with high GC had an HR of 14.73 for BF (95% CI 4.90−44.31, p<0.00001). Earlier PSA recurrence was observed in patients with high GC score that received salvage compared to adjuvant RT with median BF survival post-RT of 4.67 versus 8.78 years (p<0.04). This held true after adjusting for CAPRA-S score. Conclusions: This is the first validation of the GC in the post−RP RT setting. GC improved risk stratification above clinical classifiers. Patients with high GC received significant benefit from early RT intervention. For those patients with high pre-RT PSA and high GC, exploration of intensified therapy is warranted.

Clinical predictors for biochemical failure in patients with positive surgical margin after robotic-assisted radical prostatectomy

2021 ◽  
pp. 030089162110079
Author(s):  
Shih-Huan Su ◽  
Ying-Hsu Chang ◽  
Liang-Kang Huang ◽  
Yuan-Cheng Chu ◽  
Hung-Cheng Kan ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Cox Regression ◽  
Specific Antigen ◽  
Surgical Margin ◽  
Biochemical Failure ◽  
Positive Surgical Margin ◽  
Cox Regression Analysis ◽  
Robotic Assisted ◽  
Robotic Assisted Radical Prostatectomy

Objective: Patients with positive surgical margins (PSMs) after radical prostatectomy for localized prostate cancer have a higher risk of biochemical failure (BCF). We investigated the risk factors of BCF in patients with PSMs after robotic-assisted radical prostatectomy (RARP). Methods: We evaluated 462 patients who underwent RARP in a single medical center from 2006 through 2013. Of them, 61 with PSMs did not receive any treatment before BCF. Kaplan-Meier curve and Cox regression analysis were used to compare patients with (n = 19) and without (n = 41) BCF. Results: Overall, 13.2% of patients had PSMs, and of those, 31.7% experienced BCF during follow-up. The mean follow-up duration was 43.7 months (42.4 [non-BCF] vs 46.35 (BCF], p = 0.51). In univariant analyses, the platelet to lymphocyte ratio (6.26 [non-BCF] vs 8.02 [BCF], p = 0.04) differed statistically. When patients were grouped by pathologic grade ≦2 or ≧3 ( p = 0.004), the BCF-free survival rates differed significantly. Seminal vesicle invasion also differed significantly (5 [non-BCF] vs 7 [BCF], p = 0.005). Patients with undetectable nadir prostate-specific antigen (PSA) after RARP (BCF rate 4/34) differed statistically from those with detectable PSA after RARP (BCF rate 15/26) ( p < 0.001). In the multivariate analysis, the platelet/lymphocyte (P/L) ratio, pathologic grade, and undetectable nadir PSA remained statistically significant. Conclusions: In patients who undergo RARP and have PSMs, P/L ratio >9 preoperatively, pathologic grade ⩾3, and detectable nadir PSA after RARP should be considered adverse features. Early intervention such as salvage radiation therapy or androgen deprivation therapy should be offered to these patients.

National trends in the management of patients with positive surgical margins at the time of radical prostatectomy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 111-111 ◽  
Author(s):  
Kamyar Ghabili ◽  
Kevin Nguyen ◽  
Walter Hsiang ◽  
Jamil Syed ◽  
Alfredo Suarez-Sarmiento ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Adjuvant Therapy ◽  
Multivariable Analysis ◽  
Surgical Margins ◽  
Definitive Treatment ◽  
Management Approach ◽  
Adjuvant Radiation ◽  
Gleason Grade ◽  
Positive Surgical Margins ◽  
Pathologic Features

111 Background: The optimal management approach for patients with positive surgical margins (PSM) at radical prostatectomy (RP) has not been definitively assessed. To better understand contemporary patterns of care, we sought to examine time trends and determinants of adjuvant therapy in a large national sample of men with prostate cancer (PCa) treated with RP. Methods: We queried the National Cancer Database (NCDB) to identify men with clinically-localized PCa diagnosed from 2010 to 2014 who had PSM at RP performed as initial primary definitive treatment. We used descriptive statistics to examine subsequent management strategies, assessed as no adjuvant therapy as part of the initial planned course of management, receipt of adjuvant radiation therapy (RT), and receipt of adjuvant RT in combination with androgen deprivation therapy (ADT). Binary logistic regression models were constructed to identify patient, tumor, and facility features associated with receipt of adjuvant therapy. Results: During the study period, we identified 44,523 patients with PSM. Of those, 5,179 (11.6%) men received any adjuvant RT (+/- ADT), while only 1,380 (3%) received adjuvant RT with ADT. Use of adjuvant RT did not change over the study period ( p= 0.61). On multivariable analysis men of uninsured status (p = 0.003), Medicaid insurance (p = 0.001), and patients treated in non-academic facilities (p < 0.001) were more likely to receive adjuvant RT. In addition, use of adjuvant RT was associated with higher pre-treatment PSA (p < 0.001), pathologic stage (p < 0.001) and Gleason grade group (p < 0.001), decreasing distance from the treatment center (p < 0.001), and shorter duration between diagnosis and RP (p < 0.001). Receipt of adjuvant ADT with RT was associated with clinical and pathologic features; however, not with sociodemographic factors. Conclusions: The majority of patients experiencing PSM at RP did not receive adjuvant RT, and rates of adjuvant therapy have remained stable over time. In addition to adverse clinical and pathologic features, sociodemographic and facility factors were significantly associated with receipt of adjuvant RT; however, the addition of ADT appears largely driven by disease characteristics.

scholarly journals Prediction of a positive surgical margin and biochemical recurrence after robot-assisted radical prostatectomy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ching-Wei Yang ◽  
Hsiao-Hsien Wang ◽  
Mohamed Fayez Hassouna ◽  
Manish Chand ◽  
William J. S. Huang ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Surgical Margin ◽  
Asian Population ◽  
Nerve Sparing ◽  
Positive Surgical Margin ◽  
Robot Assisted ◽  
Surgeon Experience

AbstractThe positive surgical margin (PSM) and biochemical recurrence (BCR) are two main factors associated with poor oncotherapeutic outcomes after prostatectomy. This is an Asian population study based on a single-surgeon experience to deeply investigate the predictors for PSM and BCR. We retrospectively included 419 robot-assisted radical prostatectomy cases. The number of PSM cases was 126 (30.1%), stratified as 22 (12.2%) in stage T2 and 103 (43.6%) in stage T3. Preoperative prostate-specific antigen (PSA) > 10 ng/mL (p = 0.047; odds ratio [OR] 1.712), intraoperative blood loss > 200 mL (p = 0.006; OR 4.01), and postoperative pT3 stage (p < 0.001; OR 6.901) were three independent predictors for PSM while PSA > 10 ng/mL (p < 0.015; hazard ratio [HR] 1.8), pT3 stage (p = 0.012; HR 2.264), International Society of Urological Pathology (ISUP) grade > 3 (p = 0.02; HR 1.964), and PSM (p = 0.027; HR 1.725) were four significant predictors for BCR in multivariable analysis. PSMs occurred mostly in the posterolateral regions (73.8%) which were associated with nerve-sparing procedures (p = 0.012) while apical PSMs were correlated intraoperative bleeding (p < 0.001). A high ratio of pT3 stage after RARP in our Asian population-based might surpass the influence of PSM on BCR. PSM was less significant than PSA and ISUP grade for predicting PSA recurrence in pT3 disease. Among PSM cases, unifocal and multifocal positive margins had a similar ratio of the BCR rate (p = 0.172) but ISUP grade > 3 (p = 0.002; HR 2.689) was a significant BCR predictor. These results indicate that PSA and pathological status are key factors influencing PSM and BCR.

scholarly journals Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Residual Tumor ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

scholarly journals Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5824-5831 ◽  
Author(s):  
Ana Flávia Tibúrcio Ribeiro ◽  
Marta Pratcorona ◽  
Claudia Erpelinck-Verschueren ◽  
Veronika Rockova ◽  
Mathijs Sanders ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Gene Expression Signature ◽  
Mutation Status ◽  
Cox Regression Analysis ◽  
Prognostic Effect ◽  
Or Gene ◽  
Acute Myeloid

Abstract The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3Amutant AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3Awild-type AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3Amutant AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3Awild-type AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

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