Burden of metastatic hormone-sensitive prostate cancer to identify men more likely to benefit from early docetaxel.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 136-136 ◽  
Author(s):  
Gwenaelle Gravis ◽  
Jean-Marie Boher ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Overall Survival ◽  
De Novo ◽  
Local Treatment ◽  
Local Therapy ◽  
High Volume ◽  
Curative Intent ◽  
Consistent Effect ◽  
Visceral Metastases ◽  
Definition Of

136 Background: Patients with a low burden of metastatic disease and who relapse after localized therapy with curative intent have a longer overall survival. It is unclear whether these patients benefit from early docetaxel (D). Methods: Patients in GETUG-AFU15 (N = 385, median follow-up 84 mo) and CHAARTED (N = 790, median follow up 54 mo) were randomized to ADT alone or ADT + D and outcomes described using the same definition of high volume (HV) and low volume (LV) disease. (HV: visceral metastases and/or 4 or more bone metastases with at least one outside the axis) and whether the patients had prior local therapy or not. Results: Table 1 details across both studies that de novo HV group treated with ADT alone has the shortest overall survival and D has a consistent effect in improving OS. In contrast, in both studies patients with LV disease had a much longer OS with no evidence that D improved OS. Conclusions: There was no apparent survival benefit in CHAARTED and GETUG-15 studies with D for LV whether patients had prior local treatment or not. Across both studies, early D had a consistent effect and improved OS in HV pts especially those with no prior local therapy. Partial Support and drug supply by Sanofi. Clinical trial information: NCT00104715, NCT00309985. [Table: see text]

scholarly journals Title Does Definitive Local Therapy Offer Cure in Select HER2+ De Novo Metastatic Breast Cancer Patients Treated with Dual Anti-HER2 Blockade?

2021 ◽  
Author(s):  
Luderve Rosier ◽  
Youth Wang ◽  
Jihyun Lee ◽  
Karen Daily
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Systemic Therapy ◽  
Median Overall Survival ◽  
De Novo ◽  
Antibody Therapy ◽  
Metastatic Breast ◽  
Local Therapy ◽  
Curative Intent ◽  
Surgery Group

Abstract Purpose: The role of surgery with curative intent in HER2+ de novo metastatic breast cancer (dnMBC) is uncertain in the era of dual antibody therapy. We sought to determine from existing retrospective data current practice patterns and if an association exists between surgery to the primary tumor and improved survival in HER2+ dnMBC patients treated with dual anti-HER2 blockade, accounting for selection bias.Methods: This study employed data from the National Cancer Database (NCDB) from the years 2013 to 2015. Study inclusion was limited to adult women with HER2+ dnMBC, who received immunotherapy/biologic response modifier drugs (BRM) as a first line treatment. Patients who received both systemic therapy and surgery to the primary breast tumor and patients who received systemic therapy alone were analyzed in two groups. Chi-square test for discrete variables and Wilcox on Rank-Sum test for numeric variables was used to compare the two groups based on patient, tumor, and treatment characteristics. The primary endpoint was overall survival from the time of diagnosis to the time of death.Results: 928 women with HER2+ dnMBC treated with BRM were identified with 43.5% (n= 404) receiving surgery and 56.5% (n= 524) receiving systemic therapy alone. The 3-year overall survival was superior for the surgery group (74.1%, 95% CI 67.9-79.2%) compared to the no surgery group (53.3%; 95% CI 47.6-58.6%). The no surgery group had median overall survival of 39.8 months (95% CI 34.1-44.9), while the surgery group had not yet reached median overall survival.Conclusion: In a group of HER2+ dnMBC patients receiving systemic treatment in the era of dual antibody therapy, patients who underwent surgery had a superior 3-year survival rate than those who did not. There may be a role for HER2+ dnMBC patients with an excellent response to dual HER2 blockade to undergo curative intent local therapy to the primary tumor.

EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.

1998 ◽  
Vol 16 (4) ◽  
pp. 1248-1255 ◽  
Author(s):  
E de Alava ◽  
A Kawai ◽  
J H Healey ◽  
I Fligman ◽  
P A Meyers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Molecular Heterogeneity ◽  
Curative Intent ◽  
Adequate Treatment ◽  
Fusion Transcripts ◽  
Fusion Type

PURPOSE More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor. In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance. PATIENTS AND METHODS We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were available in 99 patients treated with curative intent. Median follow-up in these 99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate survival analyses were performed that included other prognostic factors, such as age, tumor location, size, and stage. RESULTS Among the 99 patients suitable for survival analysis, the tumors in 64 patients contained the type 1 fusion and in 35 patients contained less common fusion types. Stage at presentation was localized in 74 patients and metastatic in 25. Metastases (relative risk [RR] = 2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014) were, respectively, independent negative and positive prognostic factors for overall survival by multivariate analysis. Among 74 patients with localized tumors, the type 1 EWS-FLI1 fusion was also a significant positive predictor of overall survival (RR = 0.32; P = .034) by multivariate analysis. CONCLUSION EWS-FLI1 fusion type appears to be prognostically relevant in ES, independent of tumor site, stage, and size. Further studies are needed to clarify the biologic basis of this phenomenon.

Resection and surgically targeted radiation therapy for locally recurrent GBM.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2054-2054
Author(s):  
David Brachman ◽  
Peter Nakaji ◽  
Kris Smith ◽  
Theresa Thomas ◽  
Christopher Dardis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Local Control ◽  
Local Treatment ◽  
Post Hoc Analysis ◽  
Locally Recurrent ◽  
Targeted Radiation Therapy ◽  
Post Hoc ◽  
Recurrent Gbm

2054 Background: Recurrent GBM (rGBM) is a diffuse disease, and resection (R) alone does not provide durable local control (LC) or prolong overall survival (OS). Hypothesizing R plus immediate radiation (RT) may achieve durable LC and secondarily improve OS by permitting time for subsequent potentially effective but biologically slower treatments to have an impact, we prospectively evaluated R combined with a novel surgically targeted radiation therapy (STaRT) device utilizing Cs-131 embedded in bioresorbable collagen tiles. Methods: From 2/13-2/18 patients (pts) with locally recurrent GBM were treated on a prospective single arm trial (ClinicalTrials.gov, NCT#03088579) of maximum safe resection and immediate RT (GammaTile, GT Medical Technologies, Tempe AZ). Upon resection the at-risk areas of the surgical bed were lined with the GammaTile (GT) device, delivering 60-80 Gy at 5 mm. Follow up treatments were not specified but captured; no pt. underwent additional local therapy without progression, and no pt. was lost to follow up. We present study specified endpoints of local control (LC), overall survival (OS), and adverse events (AE), and a post hoc, hypothesis-generating analysis of outcomes by receipt of systemic (Sys) therapy. Results: 28 locally recurrent GBM were treated, 20 at first progression (range 1-3). Median age was 58 years (yrs.) (range 21-80), KPS 80 (60-100), female: male ratio 10:18 (36/64%). MGMT was methylated in 11%, unmethylated in 18%, and unknown in 71%. For all pts., median OS was 10.7 months (mo.) (range.1-42.3), and radiographic LC was 8.8 mo. (range.01-34.5). LC (defined as < 15 mm from surgical bed) was maintained in 50% of pts., and no first failure was local. 12 mo. OS was 75% for pts. < 50 yrs. vs. 43% for > 50 yrs. (HR.46, p =.009). MGMT, KPS, and sex were non-predictive. After R+GT, 17 pts. received > 1 cycle of systemic therapy (Sys), either as adjuvant or salvage, alone or in combination . Sys was bevacizumab (BEV) in 15 pts., temozolomide (TMZ) in 12, and lomustine (CCNU) in 8 (N > 17 as some pts. received > 1 Sys). Post hoc analysis disclosed a 15.1 mo. OS for pts. receiving > 1 cycle of Sys (Sys+, N = 17) vs. 6.5 mo. for no Sys (Sys-, N = 11) (hazard ratio (HR).38, p =.017)). LC was 11.4 mo. for Sys+ and 2.1 mo. for Sys- (HR.44; p =.16)). Median OS (mo.) for BEV+ vs. BEV- was 16.7/4.5 (HR.38, p =.017), for TMZ+ vs. TMZ- 17.5/6.7 (HR.40, p =.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR.61, p =.25), respectively. Three attributed AE occurred, 1 dehiscence requiring surgery and 2 radiation brain effects, medically treated. 4 unrelated deaths occurred < 60 days post-op, all in the Sys- cohort, impacting their opportunity for subsequent treatment. Conclusions: In this study local treatment alone was insufficient to achieve prolonged OS. Post hoc analysis suggests R+GT coupled with Sys may have potential to impact OS in rGBM patients. GT was FDA cleared in 2020 for use in newly diagnosed malignant and all recurrent intracranial neoplasms. Clinical trial information: NCT#03088579.

scholarly journals Local and systemic morbidities of de novo metastatic prostate cancer in Singapore: insight from 685 consecutive patients from a large prospective Uro-oncology registry

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e034331 ◽  
Author(s):  
Yu Guang Tan ◽  
Leonard Pang ◽  
Farhan Khalid ◽  
Randy Poon ◽  
Hong Hong Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Metastatic Prostate Cancer ◽  
Group Performance ◽  
De Novo ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
High Volume ◽  
Secondary Outcome ◽  
Systemic Complications

ObjectiveTo evaluate the incidence and management of local and systemic complications afflicting patients with de novo metastatic prostate cancer (mPCa) in Singapore.DesignRetrospective analysis of a large prospective Uro-oncology registry of mPCa.SettingThis study is carried out in a tertiary hospital in Singapore.ParticipantsWe reviewed our institution’s prospectively maintained database of 685 patients with mPCa over a 20-year period (1995–2014). Patients with non-mPCa or those progressed to metastatic disease after previous curative local treatments were excluded.Primary and secondary outcome measuresThe primary outcome was to evaluate the systemic and local morbidity rates associated with mPCa. Local complication was defined as the need for palliative procedures to relieve urinary obstruction, worsening renal function or refractory haematuria, while systemic complication was related to radiographic evidence of skeletal-related pathological fractures. Secondary outcomes analysed were the management and overall survival patterns over 20 years.Results237 (34.6%) patients required local palliative treatments. 88 (12.8%) patients presented with acute urinary retention, 23 patients (9.7%) required repetitive local palliative treatments. On multivariate analyses, prostate-specific antigen >100 (p=0.02) and prostate volume >50 g (p=0.03) were independent prognostic factors for significant obstruction requiring palliative procedures. 118 (17.2%) patients developed skeletal fractures, with poor Eastern Cooperative Oncology Group Performance (ECOG) status (p=0.01) and high volume bone metastasis (p<0.01) independently predictive of skeletal fractures. Altogether, 653 (95.3%) patients received androgen deprivation therapy (ADT), with the median time to castrate resistance of 21.4 months (IQR 7–27). The median overall survival was 45 months (IQR 20–63), with prostate cancer mortality of 81.4%. Improved overall survival was observed from 41.6 months (1995–1999) to 47.8 months (2010–2014) (p<0.01).ConclusionMorbidities and complications arising from mPCa are more common and debilitating than we thought, often requiring immediate palliative treatments, while many necessitate repeated interventions with progression.

Larynx preservation after initial non-cisplatin containing combination chemotherapy plus radiotherapy, as opposed to surgical intervention with or without radiotherapy in previously untreated advanced head and neck cancer: final analysis after 12 years follow-up

1993 ◽  
Vol 107 (3) ◽  
pp. 211-216 ◽  
Author(s):  
L. A. Price ◽  
H. J. Shaw ◽  
Bridget T. Hill
Keyword(s):  
Overall Survival ◽  
Combination Chemotherapy ◽  
Median Overall Survival ◽  
Postoperative Radiotherapy ◽  
Local Therapy ◽  
Final Analysis ◽  
Entire Group ◽  
Larynx Preservation

After a median follow-up of 12 years, median overall survival of 73 patients with advanced squamous cell carcinoma of the larynx was 65 months. The 61 per cent of patients responding to two courses of initial schedule A combination chemotherapy, not including cisplatin, and the 81 per cent of patients achieving a final complete remission after definitive local therapy, had median overall survival figures of 95 and 97 months respectively. Overall survival and relapse-free survival in 51 patients treated with radiotherapy only with larynx preservation, were not significantly different from the 21 patients who completed their surgery with pre- or postoperative radiotherapy: median overall figures were 71 versus 65 months. These data add weight to our proposal that use of initial combination chemotherapy followed by radiotherapy may eliminate the need for radical surgery, so preserving the larynx in patients with advanced disease, and provides evidence of some long-term benefit with 32 per cent of this entire group surviving 12 years.

Addition of Rituximab (R) to CHOP Improves Survival in the Non-GCB Subtype of Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 816-816 ◽  
Author(s):  
Pedro Farinha ◽  
Laurie Sehn ◽  
Brian Skinnider ◽  
Joseph M. Connors ◽  
Randy D. Gascoyne
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Chop Chemotherapy ◽  
Entire Study ◽  
Survival Difference

Abstract Background: The cell of origin (COO) distinction provides a prognostic and biologically relevant subclassification of DLBCL. Germinal center B cell (GCB) and non-GCB subtypes were originally characterized by gene expression studies and subsequently validated at the protein level by Hans et al., Blood 193: 275–82 (2004). The addition of R to CHOP chemotherapy has been shown to improve the outcome of patients with DLBCL. The underlying mechanism(s) responsible for this effect is largely unknown. However, it is known that R may preferentially prevent chemotherapy failure in DLBCLs that express Bcl-2 protein or fail to express Bcl-6 (Mounier et al., Blood101: 4279–84 2003, Winter et al., Blood107: 4207–13 2006). Bcl-2 over-expression and absence of Bcl-6 is more common in the non-GCB subtype. Thus, R may benefit mostly non-GCB lymphomas. To test this hypothesis we assessed the clinical impact of CHOP-R vs CHOP in DLBCL distinguished by COO subtypes. Method: We identified 163 patients with DLBCL treated with either CHOP or CHOP-R with available paraffin blocks and interpretable immuno-staining. All were de novo DLBCL cases diagnosed between 1999 and 2002 at the BCCA. The two treatment cohorts represent consecutive eras of therapy (Sehn et al., JCO2005; 23: 5027–33), and thus the median follow-up of living patients was 5.1 and 4.0 y for CHOP and CHOP-R, respectively. HIV+ patients or those with active secondary malignancies were excluded. Tissue microarrays (TMA) were built using duplicate 0.6mm cores from paraffin embedded formalin fixed (FFPE) tissues and stained with antibodies against CD10, Bcl-6, MUM1, and Bcl-2. The COO distinction was determined using the method of Hans. Results: Patients were treated with either CHOP (81) or CHOP-R (82). Their clinical characteristics, including the IPI, were evenly matched. The median follow-up of living patients was 4.4 y. The IPI was predictive of overall survival (OS) (p&lt;0.0001) for the entire study population. Six cases had uninterpretable immunostains resulting in 74 cases with a GCB phenotype and 83 with a non-GCB phenotype (n = 157). Overall, 71% and 75% of the cases over-expressed Bcl-2 and Bcl-6, respectively. Bcl-2 protein was expressed in 70% GCB cases and 73% non-GCB (p= 0.72). Bcl-6 was expressed in 96% GCB cases and 63% non-GCB cases (p&lt;0.0001). In univariate analysis, the addition of R was associated with a better prognosis in the non-GCB cases (p=0.02), but not in the GCB cases (p=0.3). This survival difference was not solely explained by either Bcl-2 or Bcl-6 expression. The addition of R to CHOP chemotherapy and IPI were independent predictors of OS in non-GCB DLBCL (p=0.02; p=0.016, respectively). The addition of R was also of prognostic importance in the lymphomas over-expressing Bcl-2 (p=0.0081). Conclusion: Immuno-chemotherapy using CHOP-R is associated with better OS in DLBCL, due largely to its effect on the non-GCB subgroup. Although Bcl-2 expression does not contribute to the determination of COO distinctions, the OS of Bcl-2-positive DLBCL patients is significantly improved by the addition of R. These results provide insight into the possible mechanisms by which R exerts its beneficial therapeutic effect. Overall Survival for 157 DLBCL Based on Cell of Origin Overall Survival for 157 DLBCL Based on Cell of Origin

ASXL1 Mutations in AML: Molecular Biomarker for Secondary AML?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2343-2343
Author(s):  
Jingmei Hsu ◽  
Anita J. Kumar ◽  
Martin P. Carroll ◽  
Noelle V. Frey ◽  
Nirav N. Shah ◽  
...  
Keyword(s):  
Overall Survival ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Myeloproliferative Neoplasm ◽  
Molecular Characteristics ◽  
Intermediate Risk ◽  
Kaplan Meier ◽  
The Impact

Abstract Background: Additional sex combs like transcription factor 1 (ASXL1) is a member of the polycomb group protein. ASXL1 mutation has been implicated in myeloid malignancy transformation. It is hypothesized that mutated ASXL1 leads to the loss of polycomb repressive complex 2 (PRC2) mediated gene repression and subsequent transforming events. Recent studies identify ASXL1 mutation as a poor prognostic marker in patients (pts) with de novo acute myeloid leukemia (AML) who present with intermediate–risk cytogenetic lesions (Patel, NEJM 2012; Schnittger, Leukemia2013). To study the impact of ASXL1 mutations in an unselected AML population, we analyzed clinical and molecular characteristics of patients with untreated AML who express ASXL1 mutation at presentation. Methods: Using next generation sequencing, 254 adult patients with AML seen at the Hospital of the University of Pennsylvania were analyzed for mutations, including ASXL1, using a 33-gene hematologic malignancy panel. Clinical characteristics were obtained from retrospective chart review. Kaplan-Meier estimates were used to calculate overall survival (OS) from time of diagnosis. Living patients were censored at date last seen. Results: ASXL1 mutations were detected in 36/254 (14%) AML pts. There were 29 known pathologic mutations, 1 benign, 1 probable pathologic, and 9 variants of unknown clinical significance (VUS). In 6/36 (16.7%) pts, ASXL1 was the sole mutation identified. Of the 30 pts with additional mutations (Figure 1), 6/30 (20%) pts harbored 2 independent ASXL1 mutations. When the 27 patients with pathologic ASCL mutations were analyzed for co-mutations, TET2 (13/27, 48%) was the most frequent ASXL1 co-mutation. FLT3 (0/27, 0%) and NPM1 (1/27, 3.7%) were notable for their absence. Median age of pts at diagnosis was 69 years (range 23-80). Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) was noted in 9/36 (25%) and 11/36 (30.6%) pts, respectively. Four pts (11.1%) had received chemotherapy and/or radiation therapy for a prior non-myeloid neoplasm. Karyotype was normal in 18/36 (50%) pts, and 7 additional pts had intermediate cytogenetic lesions. There were 7 pts (19.4%) with unfavorable cytogenetics (complex karyotype (3 pts), 7q- (3 pts), and 5q- (1 pt)). Four pts (11.1%) had a favorable karyotype, with t(8;21) in 3 pts and t(15;17) in 1 pt. At presentation, median white blood cell count (WBC) was 6.4x103/uL (1.0 x -103). In pts whose AML transformed from prior MPN, median WBC was 50 X103/uL (3.3-140). Standard induction chemotherapy with an anthracycline and cytarabine was given to 17/36 (47%) pts. An additional 3/36 (8.3%) pts underwent induction therapy with clofarabine. Complete remission (CR) was documented in 14/20 (70%) evaluable pts. Of the remaining pts, 11 received a hypomethylating agent, and 5 received other therapies. Thirty-day treatment mortality for all 36 pts and for 27 pts with known ASXL1 pathologic mutation was 13.4% and 18.5% respectively. Kaplan-Meier estimate showed a median overall survival of 349 days (median follow up of 107 days (range 15-1570)). For the 27 pts with a pathologic ASXL1 mutation, the OS was 276 days (Figure 2, median follow up of 145 days (range 18-1570)). Conclusion: ASXL1 mutations in de novo AML with intermediate-risk cytogenetics is associated with poor clinical outcome in cooperative group trials. Strikingly we demonstrate in a single institution, retrospective analysis that 66.7% of pts who present with ASXL1 mutations in the setting of previously untreated AML had documented MDS, MPN and/or prior chemotherapy/radiation. Further studies are necessary to evaluate if ASXL1 mutation has independent prognostic significance in AML or if it is primarily a marker for secondary leukemia. Figure 1: ASXL1 and co-mutations Figure 1:. ASXL1 and co-mutations Figure 2: Overall survival for AML patients with ASXL1 pathologic mutation Figure 2:. Overall survival for AML patients with ASXL1 pathologic mutation Disclosures No relevant conflicts of interest to declare.

Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA2-LBA2 ◽  
Author(s):  
Christopher Sweeney ◽  
Yu-Hui Chen ◽  
Michael Anthony Carducci ◽  
Glenn Liu ◽  
David Frasier Jarrard ◽  
...  
Keyword(s):  
High Volume ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Chemohormonal Therapy ◽  
Visceral Metastases ◽  
Skeletal Related Events ◽  
Hormone Sensitive ◽  
Ecog Ps ◽  
Clinical Trial Information

LBA2 Background: Docetaxel (D) improves OS of men with mPrCa who have progressed on androgen deprivation therapy (ADT). We aimed to assess the benefit of upfront chemohormonal therapy for metastatic PrCa. Methods: 1:1 randomization to ADT alone or ADT + D dosed 75mg/m2 every 3 weeks for 6 cycles within 4 month (mos) of starting ADT. Stratification factors: high volume (HV) vs. low volume (LV) disease (HV: visceral metastases and/or 4 or more bone metastases); anti-androgen use beyond 30 days; Age ≥70 vs. < 70 years; ECOG PS 0-1 vs. 2; Prior adjuvant ADT > 12 vs. ≤ 12 mos; FDA approved drug for delaying skeletal related events. Key eligibility criteria: suitable organ and neurological function for D; adjuvant ADT ≤ 24 mos and no progression within 12 mos of adjuvant ADT. OS was the primary endpoint and the study was powered to assess for a 33.3% improvement in median OS (80% power and 1-sided alpha=2.5%). Projected median OS for ADT alone: HV-33 mos; LV-67 mos. Results: 790 men were accrued from 7/28/06 to 11/21/2012: ADT N=393; ADT + D: N=397; balanced for demographic, stratification and disease factors. Median age: 63 years (range: 36 to 91); 98% ECOG PS 0 or 1; 89% Caucasian; 24% prior radiotherapy, 24% prior prostatectomy; HV 64% on ADT and 67% on ADT + D. Data released after 4th interim analysis in Sept 2013 when O’Brien Fleming upper boundary was crossed with 53.1% information. This report reflects 1/16/2014 data with median follow-up of 29 mos with 137 deaths on ADT alone vs. 104 deaths on ADT+D. ADT+D: Grade (G) 3/4 Neutropenic fever: 4%/2%; G3 neuropathy: 1% sensory, 1% motor; 1 death due to treatment (no deaths due to treatment on ADT). Efficacy data is in the table below. After disease progression, 123 pts on ADT alone and 45 pts on ADT + D received docetaxel. Conclusions: ADT + D improves OS over ADT alone in men with HV mPrCa. Longer follow-up is needed for men with LV mPrCa. Clinical trial information: NCT00309985. [Table: see text]

Homologous recombination deficiency (HRD): A biomarker for first-line (1L) platinum in advanced pancreatic ductal adenocarcinoma (PDAC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4132-4132 ◽  
Author(s):  
Wungki Park ◽  
Winston Wong ◽  
Kenneth H. Yu ◽  
Anna M. Varghese ◽  
Nadeem Riaz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ductal Adenocarcinoma ◽  
Clinical Implications ◽  
Genomic Profiling ◽  
First Line ◽  
Biomarker Validation ◽  
Definition Of ◽  
Platinum Chemotherapy ◽  
Prospective Database

4132 Background: HRD is an emerging biomarker for platinum therapy in PDAC. The clinical implications regarding differences in outcome between germline and somatic HRD in advanced PDAC treated with 1L platinum is unexplored. Methods: We evaluated overall survival (OS) for advanced PDAC (stage III/IV) based on their pathogenic germline (gHRD) and somatic HRD (sHRD) using integrated genomic profiling from MSK-IMPACT and 1L platinum use. HRD defined by pathogenic alterations from the following genes: BRCA1/2, PALB2, ARID1A/B/2, ATR, ATRX, ATM, BAP1, RAD50/51C/D, BRIP1, NBN, CHECK1/2, FANCA/C, CDK12, and MRE11. Results: Advanced PDAC patients (n=461) treated at MSK enrolled in a prospective database, were evaluated. Median follow-up was 27.6 months (95% CI, 24.6-30.6). Both germline and somatic profilings were available for n=350 (76%) but only somatic profiling was available for n=111 (24%). We identified n=52 patients with gHRD (11.3%), n=42 patients with sHRD (9.1%), and 48 patients with somatic VUS for HRD genes. From all 461 patients, the OS was not different between 1L non-platinum vs. 1L platinum groups (19 M vs. 19.3 M), regardleess of their HRD status. (Table) The OS was superior for gHRD vs. non-gHRD (28.7 M vs. 18.2 M), regardless of 1L treatment choice. However, similar significant OS superiority was neither observed in sHRD vs. non-sHRD, nor in VUS sHRD vs. non-VUS sHRD. In a subgroup analysis of 1L platinum treated patients, the OS was superior in gHRD vs. non-gHRD (NR vs. 17.9 M); however, there was no OS difference between sHRD and non-sHRD. Conclusions: In advanced PDAC patients, only gHRD predicted better overall survival for first-line platinum chemotherapy. These findings emphasize the importance of germline mutation testing of HRD in PDAC. Biomarker validation and functional definition of HRD such as loss of heterozygosity analysis is underway. [Table: see text]

scholarly journals Incidence and Outcomes of Pediatric Myelodysplastic Syndrome in the US

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1285-1285
Author(s):  
Ana Xavier ◽  
Matthew A. Kutny ◽  
Luciano J Costa
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndrome ◽  
Pediatric Patients ◽  
De Novo ◽  
The United States ◽  
Refractory Anemia ◽  
Histological Subtype ◽  
Risk Of Death

Background There is lack of epidemiological data on pediatric myelodysplastic syndrome (p-MDS) in the literature. MDS became reportable to the Surveillance, Epidemiology and End Results (SEER) Program in 2001, providing an opportunity to estimate the incidence and survival of pediatric patients with MDS in the United States. Methods We utilized data from the National Cancer Institute SEER-18 to determine the incidence and long term overall survival (OS) of pediatric patients (ages 0 to 20 years) diagnosed with de novo MDS or therapy-related MDS. Inclusion criteria was diagnosis of MDS (International Classification of Diseases-Oncology, Third Edition, ICD-O-4 codes 9980/3, 9991/3, 9992/3, 9982/3, 9985/3, 9983/3, 9986/3, 9986/3, 9989/3, 9985/3, 9975/3, and 9987/3) between 2001 and 2011. Follow up was updated through the end of 2011 (November 2013 submission). Overall survival was estimated using the method of Kaplan-Meier. A Cox proportional hazard model was used to compare the effects of age, race, gender, histological subtype, and etiology (de novovs. therapy-related) on survival. Results The incidence of p-MDS was 1.16 cases/1 million population*year. A greater incidence occurred in children younger than 1 year of age possibly reflecting congenital bone marrow failure syndromes (Figure 1). A total of 314 p-MDS cases were included in the analysis with median follow up of 31 months (range 0-131). Median age of patients was 9 years; 167 (53.3%) had MDS unclassifiable (NOS), 40 (12.7%) had therapy-related MDS (t-MDS), 44 (14%) had refractory anemia with excess blasts (RAEB), 32 (10.3%) had refractory anemia (RA), 17 (5.4%) had refractory cytopenia with multilineage dysplasia (RCMD), 6 (1.9%) had refractory anemia with ring sideroblasts (RARS), 5 (1.6%) had refractory anemia with excess blasts in transformation (RAEBT), and 3 (0.9%) had MDS associated with isolated del(5q). Male patients comprised 154 (49%) of cases. Racial groups included white (218, 69.4%), 52 (15.7%) black, 37 (11.8%) of other races, and 7 (2.3%) the race was unknown. The 5 year-OS for the entire cohort was 68% (95% C.I.=62.3-73.7). Patients with t-MDS had significantly worse 5 year-OS (41.2%; 95%C.I.=23.8-58.6) compared to those with de novo MDS (71.3%; 95%C.I.=65.3-77.2; P=0.004, Figure 2). In multivariate analysis of age, race, gender, histological subtype, and etiology (de novovs. therapy-related) utilizing Cox regression model, only t-MDS was associated with higher risk of death (HR=2.07, 95% C.I.=1.25-3.42, P=0.005). Conclusions Pediatric MDS is a rare disorder, with higher incidence among children younger than 1 year of age. Over two thirds of p-MDS patients will become long-term survivors, although significantly inferior outcome is seen in t-MDS. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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