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  • American Society of Clinical Oncology (ASCO)  (33)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 2515-2515
    Abstract: 2515 Background: Cytomegalovirus (CMV) antigens are present in 〉 90% of GBMs but not in normal brain making it an attractive immunological target. Methods: Highly functional autologous polyclonal CMV pp65 specific T cells were expanded under GMP-compliant conditions from GBM patients and administered after 3 weeks of lymphodepleting dose-dense temozolomide (ddTMZ, 100 mg/m 2 ). The phase I component used a 3+3 design ascending through four dose levels (5 x 10 6 cells to 1 x 10 8 cells). Treatment was repeated every 6 weeks for a total of 4 cycles. Dose expansion was conducted in recurrent GBM patients undergoing resection and in newly diagnosed GBM patients following concurrent chemoradiation. In vivo persistence and effector function of the adoptively transferred CMV-specific T cells was determined by dextramer staining and multiparameter flow cytometry in serially-sampled peripheral blood and in the tumor microenvironment. Results: 65 patients were screened, 25 underwent leukapheresis, and 20 completed at least 1 cycle. Median age 48 (27-69), 35% were MGMT methylated, and 10% were IDH mutated. No dose limiting toxicities (DLTs) observed. Complete radiographic response was observed in 1 patient, partial responses in 2, stable disease in 9, and progressive disease in 8. The median PFS time was 1.3 months (95% CI: 0-8.3 months) and the median OS time was 12 months (95% CI: 6 months to not reached). Repeated infusions of CMV-TC were associated with significant increase in circulating CMV+ CD8+ T cells, but cytokine production reflective of effector activity (CD107a, TNFα, IFNγ, IL2) was suppressed in these cells including directly from the GBM microenvironment. Conclusions: Adoptive infusion of CMV-specific T cells after lymphodepleting ddTMZ was well-tolerated. However, effector function of the adoptively transferred T cells was attenuated indicating further modulation of the T cell is required to prevent its dysfunction prior to proceeding to large scale clinical studies. Clinical trial information: NCT02661282 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 1021-1021
    Abstract: 1021 Background: At 5 years, AT did not improve disease free survival or overall survival and RS was a more accurate predictor of relapse than standard clinicopathologic characteristics for patients with hormone receptor (HR) positive tumors. Methods: A Phase III Intergroup trial tested adjuvant AT vs. AC. Women with 1-3 N + or N - and T-size 〉 1cm were randomized to 4 cycles of AT (60 mg/m 2 /60 mg/ m 2 ) or AC (60 mg/m 2 /600 mg/m 2 ) q 3 wk x 4. Patients(pts) with ER + and/ or PR + tumors received tam for 5 yrs. Pts were stratified by nodal, HR (ER+ PR+, ER+PR-, ER-PR+, ER-PR-, ER/PR unk) and menopausal status. The primary endpoint was DFS. A sample of 465 pts with HR + breast cancer with 0 to 3 positive axillary nodes who did (N =116) or did not have a recurrence had tumor tissue evaluated using the 21- gene assay. Grade and HR expression were evaluated locally and centrally. Results: 2952 pts were randomized between 7/30/98 and 1/21/00. 2883 were eligible and analyzable. Arms were balanced for age, HR, menopause, nodes, surgery, grade and T-size: median age 51; 64% ER +; 65% LN-; grade: 10% low, 38% int., 46% high; and median T-size - 2.0 cm. At a median follow-up of 11.5 years the DFS/OS results are shown in the table below. RS was a highly significant predictor of recurrence including node negative and node positive disease (P 〈 .0001) and predicted recurrence more accurately than clinical variables. Conclusions: At 11.5 yrs. median follow-up, there remains no difference in DFS or OS, although there continue to be fewer events in the AT arm in the prespecified ER/PR negative subgroup. At 10 years, the RS continues to be a more accurate predictor of relapse than standard clinical features. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 6 ( 2007-02-09), p. 669-674
    Abstract: To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. Patients and Methods Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m 2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. Results Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%). Conclusion This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 17 ( 2010-06-10), p. 2859-2867
    Abstract: Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients. Patients and Methods Two hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression. Results With a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versus-host disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk. Conclusion Allogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2010
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 12 ( 2017-04-20), p. 1341-1367
    Abstract: I am pleased to present Clinical Cancer Advances 2017, which highlights the most promising advances in patient-oriented cancer research over the past year. The report gives us an opportunity to reflect on what an exciting time it is for cancer research and how swiftly our understanding of cancer has improved. One year ago, the White House announced the national Cancer Moonshot program to accelerate progress against cancer. This shared vision of progress has reinvigorated the research community, identified new areas of scientific collaboration, and raised our ambitions regarding what may be possible beyond the progress we have already made. When I entered the field 35 years ago, I could not have imagined where we would be today. We can now detect cancer earlier, target treatments more effectively, and manage adverse effects more effectively to enable patients to live better, more fulfilling lives. Today, two of three people with cancer live at least 5 years after diagnosis, up from roughly one of two in the 1970s. This progress has resulted from decades of incremental advances that have collectively expanded our understanding of the molecular underpinnings of cancer. There is no better current example of this than ASCO’s 2017 Advance of the Year: Immunotherapy 2.0. Over the last year, there has been a wave of new successes with immunotherapy. Research has proven this approach can be effective against a wide range of hard-to-treat advanced cancers previously considered intractable. Researchers are now working to identify biologic markers that can help increase the effectiveness of treatment and determine who is most likely to benefit from immunotherapy. This knowledge will enable oncologists to make evidence-based decisions so as many patients as possible might benefit from this new type of treatment. Each successive advance builds on the previous hard work of generations of basic, translational, and clinical cancer researchers. Importantly, the advances described in this report would not have been possible without the individuals who volunteered to participate in clinical trials as part of their treatment. To turn the promising vision of a cancer moonshot into meaningful advances, we need sustained, robust federal funding for continued research and innovation. Approximately 30% of the research highlighted in this report was funded, at least in part, through federal dollars appropriated to the National Institutes of Health or the National Cancer Institute. Without this federal investment—unique internationally in scale, duration, and impact for decades—I fear we may lose the forward momentum needed to further the progress we see highlighted in this report. Federal lawmakers can further fuel progress by advancing initiatives that facilitate the use of big data to achieve the common good of high-quality care for all patients. Such programs, like ASCO’s CancerLinQ, will rapidly increase the pace of progress and dramatically expand the reach of treatment advances to the millions of patients who are living with cancer today or who will do so in the future. This investment will yield medical, scientific, economic, and societal benefits for years to come. Much work still lies ahead. Many questions remain about how cancer develops and spreads and how best to treat it. As you read through Clinical Cancer Advances 2017, I hope you are as inspired as I am by the gains the clinical cancer research community has made over the past year and by the promise of a new era of advances just over the horizon. Daniel F Hayes, MD, FASCO, FACP ASCO President, 2016 to 2017
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 6
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. 10522-10522
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. 10522-10522
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 20 ( 2017-07-10), p. 2260-2267
    Abstract: Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 25 ( 2008-09-01), p. 4063-4071
    Abstract: Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. Patients and Methods A sample of 465 patients with hormone receptor (HR) –positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Results Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P 〈 .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS ( 〈 18). Conclusion The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 33 ( 2015-11-20), p. 3938-3944
    Abstract: To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. Patients and Methods A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. Results There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). Conclusion For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15 ( 2016-05-20), p. 1824-1825
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15 ( 2016-05-20), p. 1824-1825
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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