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  • American Society of Clinical Oncology (ASCO)  (5)
  • 1
    Online Resource
    Online Resource
    Burkitt Lymphoma International Prognostic Index
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 10 ( 2021-04-01), p. 1129-1138
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 10 ( 2021-04-01), p. 1129-1138
    Abstract: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase 〉 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.03288
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Phase I drug-interaction study of effects of calcium and magnesium infusions on oxaliplatin pharmacokinetics and acute neurotoxicity in colorectal cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 3_suppl ( 2014-01-20), p. 578-578
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 578-578
    Abstract: 578 Background: Calcium and magnesium (Ca/Mg) infusions have been suggested as an effective intervention for preventing oxaliplatin-induced neurotoxicity, but the effects of Ca/Mg infusions on oxaliplatin pharmacokinetics, motor nerve hyperexcitability, and acute neurotoxicity symptoms are unclear. Methods: In this double-blind crossover study, colorectal cancer patients undergoing oxaliplatin-based chemotherapy were randomised to receive Ca/Mg (1g Ca Gluconate plus 1g MgSO 4 ) on cycle 1 and placebo (vehicle alone) on cycle 2, or to receive the same treatments in the opposite sequence. Study endpoints included plasma pharmacokinetics of intact oxaliplatin and free platinum; electromyography (EMG) detection of abnormal spontaneous high-frequency motor unit action potential discharges; and patient-reported acute neurotoxicity symptoms and their preferred study treatment for reducing these symptoms. Results: The planned accrual target was achieved. Nineteen of 20 enrolled patients completed the study. Plasma pharmacokinetics of intact oxaliplatin and free platinum were similar when oxaliplatin was given with Ca/Mg or placebo (ratio of geometric means of AUC 0-t with Ca/Mg or placebo: intact oxaliplatin, 0.95 (90% CI, 0.90 – 1.01); free platinum, 0.99 (90% CI, 0.94 – 1.05)). EMG motor nerve hyperexcitability scores were similar with Ca/Mg and placebo (mean difference in EMG score between Ca/Mg and placebo: -0.3 (95% CI, -2.2 – 1.6)). Patient-reported acute neurotoxicity symptoms were similar in frequency with Ca/Mg and placebo. For reducing neurotoxic symptoms, fewer patients preferred Ca/Mg than placebo or neither treatment (26% versus 74%; p 〈 0.01). Conclusions: Ca/Mg infusions do not alter the clinical pharmacokinetics of oxaliplatin and do not seem to reduce its acute neurotoxicity. Clinical trial information: ACTRN12611000738921.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.3_suppl.578
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    The Ave-Rec trial: Phase II trial of PD-L1/PD-1 blockade with avelumab plus chemoradiotherapy for locally advanced resectable T3B-4/N1-2 rectal cancer—Toxicity and interim efficacy data.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 3616-3616
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 3616-3616
    Abstract: 3616 Background: Neoadjuvant long course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) results in a complete pathological response rate in 10-30% of patients (pts), but with 20-40% non-responders and 10-15% have local recurrence. Radiotherapy (RT) is immuno-stimulatory by enhancing local/distant tumour cell death, but also immunosuppressive as it stimulates PDL1 production and myeloid-derived suppressor cell activity. Hence PDL1 inhibition may be required to enhance the immuno-stimulatory effects of RT. Hypothesis: In pts with resectable LARC, the anti-PDL1 antibody Avelumab given post LCCRT may enhance the pathological/imaging response rates whilst reducing local/distant relapse rates. Methods: Phase II single arm trial. All pts had standard LCCRT (50.4Gy RT plus 5FU [225mg/m 2 /day/CI] or Capecitabine [825mg/m 2 BID on days of RT] over 5.5 weeks). Post LCCRT (prior to surgery), pts received 4 cycles Avelumab (AV) (10mg/kg, q2 weeks), then surgical resection at 10-12 weeks post LCCRT. Fresh tumour biopsy and ctDNA sampling taken pre LCCRT, pre Cycle 1 AV and at surgery. Response by FDG PET/CT and pelvic MRI at 8 weeks post LCCRT, pre surgery. Inclusion Criteria: pts with LARC (MRI stage T3b-4/N1-2/M0), planned for LCCRT followed by curative resection, tumoural lower border within 12cm from anal verge, measurable disease (RECIST1.1), ECOG 0-1, adequate organ function and no contraindications to AV therapy. Endpoints: (a) Primary; Complete pathological response rate post-LCCRT (Target ≥ 35%), documented by central pathologist, (b) Secondary; MRI and FDG PET/CT imaging responses by RECIST1.1 and PERCIST, respectively. Toxicity. (c) Exploratory; Tumoural immune cell subsets/checkpoint expression (by multiplex immunohistochemistry and in-vitro functional assays) and ctDNA analysis. Distant relapse-free survival and the sites of relapse. ANZCTR : NCT03299660. Results: 37 pts across 6 sites, with 33 patients (89%) received allocated interventions: LCCRT, AV and surgery (where possible). Age median 55 years (31-76). M:F 23:10. Baseline tumoural stage: T3b-d 75%, T4a-b 25%. No pts with dMMR/MSI-H tumour. Overall 33 pts completed LCCRT, 31 pts (83%) completed all 4 cycles of AV and 32 pts (86%) had planned surgery (22, ULAR, 2 APR, 2 AR, 6 Other). ORR Pelvic MRI presurgery (N = 33): 2 CR, 14 PR, and 31 DCR. FDG PET/CT (N = 31): 10 CMR, 18 PMR and 3 SMD. Overall 10 pts Grade 3/4 AEs, with 15 G3/4 events. Only 3 pts with treatment-related G3 and no G4 AEs. No specific immune-related G3 AEs observed. Post-operative complications were not unexpected. Conclusions: Consolidation Avelumab post LCCRT for pts with LARC, was well tolerated with promising activity. Pathological response, biological substudies (immunological and ctDNA) and survival endpoints to be reported. Clinical trial information: NCT03299660 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.3616
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 10 ( 2018-04-01), p. 1020-1044
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 10 ( 2018-04-01), p. 1020-1044
    Abstract: I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors’ genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients’ own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy—a type of adoptive cell immunotherapy—has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation’s support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal research investment to accelerate the discovery of the next generation of cancer treatments. Another major trend in this year’s report is progress in precision medicine approaches to treat cancer. Although precision medicine offers promise to people with cancer and their families, that promise is only as good as our ability to make these treatments available to all patients. My presidential theme, “Delivering Discoveries: Expanding the Reach of Precision Medicine,” focuses on tackling this formidable challenge so that new targeted therapies are accessible to anyone who faces a cancer diagnosis. By improving access to high-quality care, harnessing big data on patient outcomes from across the globe, and pursuing innovative clinical trials, I am optimistic that we will speed the delivery of these most promising treatments to more patients. Sincerely, Bruce E. Johnson, FASCO ASCO President, 2017 to 2018
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.77.0446
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    KRAS and BRAF Mutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial
    American Society of Clinical Oncology (ASCO) ; 2009
    In:  Journal of Clinical Oncology Vol. 27, No. 35 ( 2009-12-10), p. 5931-5937
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 35 ( 2009-12-10), p. 5931-5937
    Abstract: Activating mutation of the KRAS oncogene is an established predictive biomarker for resistance to anti–epidermal growth factor receptor (anti-EGFR) therapies in advanced colorectal cancer (aCRC). We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies. Patients and Methods The Medical Research Council Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing (MRC FOCUS) trial compared treatment sequences including first-line fluorouracil (FU), FU/irinotecan or FU/oxaliplatin in aCRC. Tumor blocks were obtained from 711 consenting patients. DNA was extracted and KRAS codons 12, 13, and 61 and BRAF codon 600 were assessed by pyrosequencing. Mutation (mut) status was assessed first as a prognostic factor and then as a predictive biomarker for the benefit of adding irinotecan or oxaliplatin to FU. The association of BRAF-mut with loss of MLH1 was assessed by immunohistochemistry. Results Three hundred eight (43.3%) of 711 patients had KRAS-mut and 56 (7.9%) of 711 had BRAF-mut. Mutation of KRAS, BRAF, or both was present in 360 (50.6%) of 711 patients. Mutation in either KRAS or BRAF was a poor prognostic factor for overall survival (OS; hazard ratio [HR], 1.40; 95% CI, 1.20 to 1.65; P 〈 .0001) but had minimal impact on progression-free survival (PFS; HR, 1.16; 95% CI, 1.00 to 1.36; P = .05). Mutation status did not affect the impact of irinotecan or oxaliplatin on PFS or OS. BRAF-mut was weakly associated with loss of MLH1 staining (P = .012). Conclusion KRAS/BRAF mutation is associated with poor prognosis but is not a predictive biomarker for irinotecan or oxaliplatin. There is no evidence that patients with KRAS/BRAF mutated tumors are less likely to benefit from these standard chemotherapy agents.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2009.22.4295
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2009
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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