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  • American Society of Clinical Oncology (ASCO)  (91)
  • 1
    In: JCO Clinical Cancer Informatics, American Society of Clinical Oncology (ASCO), , No. 4 ( 2020-11), p. 1027-1038
    Abstract: Image analysis is one of the most promising applications of artificial intelligence (AI) in health care, potentially improving prediction, diagnosis, and treatment of diseases. Although scientific advances in this area critically depend on the accessibility of large-volume and high-quality data, sharing data between institutions faces various ethical and legal constraints as well as organizational and technical obstacles. METHODS The Joint Imaging Platform (JIP) of the German Cancer Consortium (DKTK) addresses these issues by providing federated data analysis technology in a secure and compliant way. Using the JIP, medical image data remain in the originator institutions, but analysis and AI algorithms are shared and jointly used. Common standards and interfaces to local systems ensure permanent data sovereignty of participating institutions. RESULTS The JIP is established in the radiology and nuclear medicine departments of 10 university hospitals in Germany (DKTK partner sites). In multiple complementary use cases, we show that the platform fulfills all relevant requirements to serve as a foundation for multicenter medical imaging trials and research on large cohorts, including the harmonization and integration of data, interactive analysis, automatic analysis, federated machine learning, and extensibility and maintenance processes, which are elementary for the sustainability of such a platform. CONCLUSION The results demonstrate the feasibility of using the JIP as a federated data analytics platform in heterogeneous clinical information technology and software landscapes, solving an important bottleneck for the application of AI to large-scale clinical imaging data.
    Type of Medium: Online Resource
    ISSN: 2473-4276
    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. 34, No. 25 ( 2016-09-01), p. 3054-3061
    Abstract: Survival after metastatic cancer has improved at the cost of increased presentation with metastatic spinal disease. For patients with pathologic spinal fractures and/or spinal cord compression, surgical intervention may relieve pain and improve quality of life. Surgery is generally considered to be inappropriate if anticipated survival is 〈 3 months. The aim of this international multicenter study was to analyze data from patients who died within 3 months or 2 years after surgery, to identify preoperative factors associated with poor or good survival, and to avoid inappropriate selection of patients for surgery in the future. Patients and Methods A total of 1,266 patients underwent surgery for impending pathologic fractures and/or neurologic deficits and were prospectively observed. Data collected included tumor characteristics, preoperative fitness (American Society of Anesthesiologists advisory [ASA]), neurologic status (Frankel scale), performance (Karnofsky performance score [KPS] ), and quality of life (EuroQol five-dimensions questionnaire [EQ-5D]). Outcomes were survival at 3 months and 2 years postsurgery. Univariable and multivariable logistic regression analyses were used to find preoperative factors associated with short-term and long-term survival. Results In univariable analysis, age, emergency surgery, KPS, EQ-5D, ASA, Frankel, and Tokuhashi/Tomita scores were significantly associated with short survival. In multivariable analysis, KPS and age were significantly associated with short survival (odds ratio [OR], 1.36; 95% CI, 1.15 to 1.62; and OR, 1.14; 95% CI, 1.02 to 1.27, respectively). Associated with longer survival in univariable analysis were age, number of levels included in surgery, KPS, EQ-5D, Frankel, and Tokuhashi/Tomita scores. In multivariable analysis, the number of levels included in surgery (OR, 1.21; 95% CI, 1.06 to 1.38) and primary tumor type were significantly associated with longer survival. Conclusion Poor performance status at presentation is the strongest indicator of poor short-term survival, whereas low disease load and favorable tumor histology are associated with longer-term survival.
    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
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. TPS3620-TPS3620
    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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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO)
    Abstract: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. METHODS Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0). RESULTS We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment. CONCLUSION The revised RANO 2.0 criteria refine response assessment in gliomas.
    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: 2023
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. TPS3647-TPS3647
    Abstract: TPS3647 Background: Observational data indicate that physical activity (PA) is strongly associated with colon-cancer specific survival. NCIC CTG CO.21 (CHALLENGE) is designed to determine the effects of a structured PA intervention on disease-control outcomes for survivors of high-risk stage II or III colon cancer who have completed adjuvant chemotherapy within the previous 2-6 months. Methods: Phase III randomized controlled trial. Target sample size of 962 patients is powered to detect a Hazard Ratio of 0.75 for disease-free survival (DFS). Trial participants will be stratified by centre, disease stage, body mass index, and performance status, and will be randomly assigned to a structured, individualized PA intervention or to general health education materials. The PA intervention will consist of a behavioural support program and supervised PA sessions delivered over a 3-year period, beginning with regular face-to-face sessions and tapering to less frequent face-to-face or telephone sessions. The goal of the PA program is to increase weekly PA by 10 MET hours/week. The PA program is delivered by physical activity consultants trained in exercise physiology and behavior change. Outcomes: The primary endpoint is DFS. Important secondary endpoints include multiple patient-reported outcomes (including those that address fatigue), objective physical functioning, biologic correlative markers (including assessment of the insulin pathway), and an economic analysis. Current Enrollment: The study is open at 19 centers in Canada and 20 centers in Australia. Accrual as of February 4, 2013 includes 212 registered and 184 randomized patients. Summary: Cancer survivors and cancer care professionals are interested in the potential role of PA to improve multiple disease-related outcomes, but a randomized controlled trial is needed to provide compelling evidence to justify changes in health care policies and practice. Clinical trial information: NCT00819208.
    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: 2013
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 31 ( 2014-11-01), p. 3490-3496
    Abstract: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. Patients and Methods We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. Results For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, −9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P 〈 .001) and need for hospitalization (P 〈 .001), and preserved quality of life (P = .04). Conclusion For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life.
    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: 2014
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS7078-TPS7078
    Abstract: TPS7078 Background: Fosciclopirox (CPX-POM) is a broad-spectrum anticancer agent being developed through a public-private partnership between CicloMed LLC and KU Cancer Center (KUCC). Following intravenous administration, fosciclopirox is rapidly and completely metabolized to its active metabolite ciclopirox (CPX). Given fosciclopirox is a prodrug lacking pharmacologic activity, in vitro mechanistic studies were conducted utilizing CPX as the test article. In collaboration with Notable Labs (Foster City CA), we characterized ex vivo sensitivity to CPX in bone marrow and peripheral blood samples from ten newly diagnosed and relapsed acute myeloid leukemia (AML) patients. Reductions in blast counts were seen in each of the 10 patients studied at clinically relevant concentrations. In vitro experiments in AML cell lines (HL-60 and MV4-11) characterized the mechanism(s) of the anti-leukemia activity of CPX. CPX inhibited proliferation of AML cell lines in a dose- and time-dependent manner with IC50 values ranging from 2.5-4 µM. CPX induced cell cycle arrest in the subG0 phase and CPX-treated cells lost their ability to enter to G0-G1 phase. Moreover, CPX induced early and late phase apoptosis. CPX also activated Caspase 3/7 activity. This preclinical data led to the development of a multi-center Phase 1B/2A clinical proof of concept trial (NCT04956042) in AML patients. Methods: Eligible AML patients are adults with primary refractory (two prior regimens) or relapsed AML; ECOG PS 0-2; adequate end organ function. Prior allogeneic stem cell transplant is allowed if patient is more than 100 days post-transplant with no active graft-versus-host disease. CPX-POM is administered as 900 mg/m2 once daily as an IV infusion on Days 1 to 5 of each 21-day cycle. Day 8 bone marrow sample is collected for correlative studies. Ex vivo Drug Sensitivity Screening (DSS) will be performed on samples obtained prior to treatment and C1 Days 8 and 21. 14 evaluable patients will be enrolled in Cohort 1a. If disease response is observed in at least 4 of 14 patients, an additional 14 patients will be enrolled in Cohort 1b. During Cohort 1a, patients who do not respond to CPX-POM alone may be switched to the combination of CPX-POM + cytarabine. Patients who respond to the combination treatment may continue until evidence of disease progression. If disease response to CPX-POM alone is not observed in at least 4 of 14 patients in Cohort 1a, the study may be terminated or a Cohort 2a may be initiated using the combination of CPX-POM and cytarabine. The trial is currently open at two sites with 14 patients enrolled and 8 evaluable for the primary endpoint. Clinical trial information: NCT04956042 .
    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: 2023
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 3 ( 2023-01-20), p. 517-527
    Abstract: Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma. PATIENTS AND METHODS In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level 〈 1% subgroup. RESULTS At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression 〈 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients. CONCLUSION Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment.
    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: 2023
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS8585-TPS8585
    Abstract: TPS8585 Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide highlighting the importance of improving current therapeutic options. In particular, elderly and frail patients are not only underrepresented in clinical trials, but also frequently do not receive standard treatment regimens due to comorbidities. For example, patients with unresectable stage III NSCLC who are unfit for chemotherapy (CHT) do not benefit from the recent seminal therapy algorithm change for this disease, i.e. consolidation therapy with the immune checkpoint inhibitor (ICI) durvalumab after combined radiochemotherapy (RChT). Instead, these patients are treated with radiotherapy only, raising the serious concern of undertreatment. This issue is addressed by the TRADE-hypo clinical trial that investigates a novel therapy option for NSCLC stage III patients not capable of receiving CHT. To this end, thoracic radiotherapy (TRT) is administered together with durvalumab, employing the synergism created by the combination of restoring anti-tumor immune response by the ICI with the induction of immunogenicity by irradiation. The latter effect has been suggested to be further boosted by hypofractionated radiotherapy, which could also be more practicable for the patient. Taken these considerations into account, the TRADE-hypo trial addresses safety and efficacy of durvalumab therapy combined with either conventional or hypofractionated TRT. Methods: The TRADE-hypo trial is a prospective, randomized, open-label, multicentric phase II trial. Eligible patients are diagnosed with unresectable stage III NSCLC and not capable of receiving sequential RChT due to high vulnerability as reflected by a poor performance status (ECOG 2 or ECOG1 and CCI≥ 1) and/or high age (≥ 70)]. Two treatment groups are evaluated: Both receive durvalumab (1,5000 mg, Q4W) for up to 12 months. In the CON-group this is combined with conventionally fractionated TRT (30 x 2 Gy), while in the HYPO-group patients are treated with hypofractionated TRT (20 x 2.75 Gy). In the HYPO-arm, a safety stop-and-go lead-in phase precedes full enrollment. Here, patients are closely monitored with regard to toxicity (i.e., pneumonitis grade ≥ 3 within 8 weeks after TRT) in small cohorts of 6. The primary objective of the trial is safety and tolerability. As a primary efficacy endpoint, the objective response rate after 3 months will be evaluated. Further endpoints are additional parameters of safety and efficacy, as well as the comprehensive collection of biomaterials to be analyzed regarding treatment-induced changes and potential novel biomarkers. As of February 10, 2021, 9 patients of planned 88 patients have been enrolled in the TRADE-hypo trial. Clinical trial information: NCT04351256.
    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: 2021
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 6 ( 2009-02-20), p. 851-856
    Abstract: Preoperative chemotherapy is an accepted standard in the treatment of localized esophagogastric adenocarcinoma. Adding radiation therapy to preoperative chemotherapy appears promising, but its definitive value remains unknown. Patients and Methods Patients with locally advanced (uT3-4NXM0) adenocarcinoma of the lower esophagus or gastric cardia were randomly allocated to one of two treatment groups: induction chemotherapy (15 weeks) followed by surgery (arm A); or chemotherapy (12 weeks) followed by chemoradiotherapy (3 weeks) followed by surgery (arm B). Primary outcome was overall survival time. A total of 354 patients were needed to detect a 10% increase in 3-year survival from 25% to 35% by addition of radiation therapy. The study was prematurely closed due to low accrual. Results The median observation time was 46 months. A total of 126 patients were randomly assigned and 119 eligible patients were evaluated. The number of patients undergoing complete tumor resection was not different between treatment groups (69.5% v 71.5%). Patients in arm B had a significant higher probability of showing pathologic complete response (15.6% v 2.0%) or tumor-free lymph nodes (64.4% v 37.7%) at resection. Preoperative radiation therapy improved 3-year survival rate from 27.7% to 47.4% (log-rank P = .07, hazard ratio adjusted for randomization strata variables 0.67, 95% CI, 0.41 to 1.07). Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group (10.2% v 3.8%; P = .26). Conclusion Although the study was closed early and statistical significance was not achieved, results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction.
    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: 2009
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