feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Society of Clinical Oncology (ASCO)  (14)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 27 ( 2006-09-20), p. 4499-4506
    Abstract: To improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone). Patients and Methods Four hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy. Results Four hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P = .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%). Conclusion Overall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2006
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 5058-5058
    Abstract: 5058 Background: Castration-resistant prostate cancer (CRPC) is the lethal form of the disease. One of the principal therapies in CRPC is the potent androgen receptor (AR) signaling inhibitor enzalutamide (enza). Most patients benefit from enza, but disease progression is nearly universal. A variety of resistance mechanisms have been described by comparing enza-naïve and enza-resistant tumors. However, these results are largely from different groups of patients and do not provide information on the changes induced by enza within a given patient. Lineage plasticity—most commonly-exemplified by loss of AR signaling and switch from a luminal to an alternate differentiation program—is a particularly aggressive resistance mechanism. Importantly, lineage plasticity appears to be increasing in incidence since more widespread use of potent AR signaling inhibitors such as enza. To improve our understanding of resistance mechanisms induced by enza treatment, we analyzed the transcriptomes of matched metastatic CRPC patient biopsies obtained prior to treatment and at the time of disease progression. Methods: All biopsies were obtained as part of the Stand Up 2 Cancer/Prostate Cancer Foundation-funded West Coast Dream Team, a prospective, IRB-approved protocol focused on understanding the biology of metastatic CRPC. We identified 21 patients for whom matched tumor biopsies with RNA-seq were available prior to starting treatment with enza and at the time of progression while still taking enza. Results: Our RNA-seq analysis demonstrates that the majority of progression tumors cluster with their baseline pair, suggesting that enza does not markedly change the tumor transcriptome in most cases. Three of 21 patients showed evidence of lineage plasticity at progression by gene expression analysis. By analyzing the RNA-seq data, we identified pathways linked to stemness that were more activated in baseline tumors from patients whose progression tumors underwent lineage plasticity. Furthermore, we identified a gene signature enriched in these baseline tumors that was associated with risk of lineage plasticity after enza treatment. We determined that high expression of this signature was strongly associated with poor survival from the time of AR signaling inhibitor treatment in independent patient samples, suggesting this signature is linked to poor patient outcome. Conclusions: Enza-resistant tumors are heterogeneous. Most tumors do not undergo significant transcriptional changes at progression vs. baseline. Matching recent reports, approximately 15% of tumors underwent lineage plasticity upon progression. Our work implicates a gene program that may predispose tumors to enza-induced lineage plasticity. Finally, the gene signature we identified may be a marker of lineage plasticity risk and tumor aggressiveness in CRPC prior to the initiation of AR signaling inhibitor therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 339-339
    Abstract: 339 Background: Stereotactic Body Radiotherapy (SBRT) delivers high dose per fraction radiotherapy to targets with high precision. Such hypofractionated RT appears to act as an immune adjuvant, altering the tumor infiltrating immune landscape and enriching it for lymphocytes as numerous preclinical investigations would suggest. Based on this hypothesis, hundreds of ongoing trials listed in clinicaltrials.gov currently test the combination of RT (largely SBRT) with various immunotherapies. However, studies directly measuring the representation of infiltrating immune cells after SBRT in patients are few and far between and none exist in the context of prostate cancer. We therefore sought to interrogate the tumor-immune interface after prostate SBRT using fresh tissue in patients. Methods: Fresh prostate tissue from patients (N=10) enrolled in a clinical trial of prostate SBRT (three fractions of 8 Gy directed to the prostate and seminal vesicles) in the neoadjuvant setting two weeks prior to radical prostatectomy was subjected to multicolor flow cytometry and compared to that of Gleason Grade and T stage matched controls who did not undergo neoadjuvant therapy. Results: With a threshold of significance level of 0.05 for unadjusted p-values, using two-sided two-sample t-test, myeloid cells and particularly CD14 +/hi CD16 + DR + intermediate monocytes/macrophages were enriched, while lymphocytes, including T cells and CD56 + 16 − NK cells were decreased in SBRT-treated prostates as compared to unirradiated controls. Conclusions: The immune infiltrates in prostates two weeks after SBRT demonstrates a significant lymphoid to myeloid shift consistent with a tumor microenvironment after SBRT that is likely immunosuppressive beyond what can be targeted through the PD-1/L1 or CTLA-4 axis alone. This may have implications for the design of immunotherapy trials, especially in prostate cancer, that test SBRT in combination with immunotherapies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 29 ( 2014-10-10), p. 3264-3274
    Abstract: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown. Patients and Methods In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non–mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC). Results Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response. Conclusion AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4 ( 2023-02-01), p. 881-892
    Abstract: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality. RESULTS Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points ( P interaction 〈 .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P 〈 .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P 〈 .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 211-211
    Abstract: 211 Background: Low-volume de novo metastatic hormone-sensitive prostate cancer (mHSPC) has historically been treated with lifelong androgen deprivation therapy (ADT). Recently, however, the addition of several advanced therapeutic options – radiation therapy (RT) to the primary, advanced hormonal therapy agents such as abiraterone acetate/prednisone (AAP), and chemotherapy – to ADT have been shown to improve survival in low-volume mHSPC. The objective of this study was to compare the cost-effectiveness of treating low-volume mHSPC patients upfront with RT+ADT, AAP+ADT, or docetaxel+ADT. Methods: A Markov-based cost-effectiveness analysis was constructed comparing three treatment strategies for low-volume mHSPC patients: (1) upfront RT+ADT -- 〉 salvage AAP+ADT -- 〉 salvage docetaxel+ADT; (2) upfront AAP+ADT -- 〉 salvage docetaxel+ADT, and (3) upfront docetaxel+ADT -- 〉 salvage AAP+ADT. Transition probabilities were calculated using data from STAMPEDE arms C/G/H, COU-AA-301, COU-AA-302, and TAX-327. RT was delivered via five-fraction stereotactic body radiation therapy. The analysis utilized a 10-year time horizon, and a $100,000/quality adjusted life year (QALY) willingness-to-pay threshold. Utilities were extracted from the literature; costs were taken from Medicare fee schedules and VA oral drug contracts. Results: At 10 years, total cost was $140K, $259K, and $189K, with total QALYs of 4.66, 5.03, and 3.72 for strategies (1) upfront RT+ADT, (2) upfront AAP+ADT, and (3) upfront docetaxel+ADT, respectively. Compared to upfront RT+ADT, upfront AAP+ADT was not cost-effective (ICER: $321K/QALY). This result remained unchanged even after modification of various model inputs in 1-way sensitivity analysis. Upfront docetaxel+ADT was both more costly and less effective than upfront RT+ADT (ICER: -$53K/QALY). Conclusions: At 10 years, RT+ADT is cost-effective compared to other advanced systemic therapy options alone, and should be considered as a viable treatment strategy in all patients with a low-burden of metastatic disease. Additional studies are needed to determine whether any benefit exists in combining RT to the primary with upfront advanced systemic therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 348-348
    Abstract: 348 Background: In the European Union (EU) differences in tumor incidence for urothelial cell carcinoma (UCC) have been reported. Besides occupational exposure, tobacco smoke and nitrite have been identified as risk factors for UCC. No study has evaluated the regional incidence of UCC in Germany in consideration of socioeconomic landscape. We investigated if a different allocation to agriculture (A), industrial use (I) and land settlement (S) are associated with the incidence of UCC. Methods: In collaboration with the German Centre for Cancer Registry Data, Robert Koch Institute, Berlin, all new cases of UCC between 2003 and 2010 were included, with partly dropped out information due to incomplete reporting. Kulldorff spatial cluster test was used to detect clusters with high incidence rates. Furthermore, information within the different administrative areas of Germany from 2010 for land use factors A, I and S were obtained from the Regional Database Germany, and calculated as both, a proportion of the total area of the respective administrative region and as a smoothed proportion including values from neighbouring regions. A negative binomial model was used to test the association of the area information in addition to the expected cases information for age and sex distribution. All tests were two-sided and a significance level of α=5% was used. Results: In a follow up of 437,847,835 person years, 171,086 incident cases of UCC were identified. Cluster analysis revealed areas with a significant higher incidence of UCC than others (p=0.0002). Multivariate analysis on land use (as smoothed proportion) in all available counties showed that each such factor is an independent risk factor for UCC (p 〈 0.00001, respectively). The interquartile range of the respective proportions and the relative risk (RR) for raising the respective proportion from first to third quantile of different land use were 35%-60% (RR 1.10), 0.5%-2.3% (RR 1.07) and 10%-29% (RR 1.21) for all three factors A, I, and S, respectively. Conclusions: This study displays regional differences in UCC incidence in Germany. Furthermore, results suggest that environmental exposure based on socioeconomic factors may present a relevant carcinogenic risk for UCC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: JCO Clinical Cancer Informatics, American Society of Clinical Oncology (ASCO), , No. 1 ( 2017-11), p. 1-6
    Abstract: Salvage radiotherapy (SRT) is the standard of care offered when postprostatectomy prostate-specific antigen (PSA) levels are ≥ 0.2 ng/mL. However, emerging evidence suggests that early SRT (ie, SRT delivered at PSA values 〈 0.2 ng/mL, but generally ≥ 0.05 ng/mL) improves oncologic outcomes. We evaluated the feasibility of improving referral rates for discussion of early SRT by using a dynamic registry that identifies through the electronic medical record patients with rising postprostatectomy PSA levels. Methods We developed an iteratively updated registry that identifies patients who fall within two postoperative PSA strata: ≥ 0.05 to 〈 0.1 ng/mL and ≥ 0.1 to 〈 0.2 ng/mL. We compared referral rates to radiation oncology during a 3-year period before use of this registry with those during a 1-year period after promotion of the registry in multidisciplinary tumor board settings. Results Before promotion of the registry, referral rates for patients with PSA values ≥ 0.05 to 〈 0.1 ng/mL and ≥ 0.1 to 〈 0.2 ng/mL were 35% and 65%, respectively. After promotion of the registry, referral rates within each stratum increased significantly to 82% and 94%, respectively ( P 〈 .05 for both by Fisher’s exact test). The overall rate of referral for patients with PSA values ≥ 0.05 to 〈 0.2 ng/mL rose from 48% to 90% ( P 〈 .001). Conclusion The creation of a registry of patients with rising postprostatectomy PSA values can facilitate increased referral rates for early SRT without burdening providers with a clinical support tool embedded within the EMR itself. This is true even in the case of already high baseline rates of referral for early SRT. The changes reported herein most likely reflect a Hawthorne effect wherein the ability to track referrals rather than a direct function of the registry influenced practice patterns. Nonetheless, the registry provided an integral framework to allow for tracking.
    Type of Medium: Online Resource
    ISSN: 2473-4276
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO)
    Abstract: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R 2 ). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79] ; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61] , respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94] ) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92] ; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61] , respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R 2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 53-53
    Abstract: 53 Background: The costs of treating localized, Gleason score 9 and 10 prostate cancer remain poorly described, especially when the particularly aggressive nature of the disease often requires a multimodal approach. We report the results of time-driven activity-based costing to assess the long-term costs of treating this subset of patients with either RALP, high-dose EBRT, or EBRT with a high-dose rate brachytherapy (BT) boost. Methods: Based on a multi-institutional cohort of 487 patients with Gleason score 9-10 prostate cancer, we generated process maps for each phase of care from the initial urologic visit through a median follow-up of 3.76 years, incorporating all prostate cancer treatment over this horizon. Costs were calculated per unit time, and the proportion of capacity for each step was determined. TDABC was defined as the sum of its resources. Results: Substantial cost variation was demonstrated between treatment modalities with an estimated median cost of $49,681 for EBRT, $35,140 for RALP, and $31,647 for EBRT + BT at 3.76 years. The primary driver in cost variation was the use of ADT. RALP (170 pts) ranged from $18,896 (29.5%) for no postoperative therapy to $63,270 for immediate long-term ADT (5.3%). EBRT (230 pts) had the greatest cost variation [Table 1] . Finally, EBRT + BT (336 pts) ranged from $26,522 for EBRT + BT alone (12.6%) to $37,834 for EBRT + BT + salvage ADT + HIFU (1.2%). Conclusions: Characterizing the costs associated with the distribution of treatments for men with high-risk prostate cancer is essential as we move towards health care accountability. There is substantial long-term cost variation between treatments in this subset of patients, and understanding these differences may affect treatment implications as we shift toward accountable payment models.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages