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  • 1
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 369, No. 6499 ( 2020-07-03)
    Abstract: Cancer treatments are often more successful when the disease is detected early. We evaluated the feasibility and safety of multicancer blood testing coupled with positron emission tomography–computed tomography (PET-CT) imaging to detect cancer in a prospective, interventional study of 10,006 women not previously known to have cancer. Positive blood tests were independently confirmed by a diagnostic PET-CT, which also localized the cancer. Twenty-six cancers were detected by blood testing. Of these, 15 underwent PET-CT imaging and nine (60%) were surgically excised. Twenty-four additional cancers were detected by standard-of-care screening and 46 by neither approach. One percent of participants underwent PET-CT imaging based on false-positive blood tests, and 0.22% underwent a futile invasive diagnostic procedure. These data demonstrate that multicancer blood testing combined with PET-CT can be safely incorporated into routine clinical care, in some cases leading to surgery with intent to cure.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 3037-3037
    Abstract: 3037 Background: Less than 20% of cancers are diagnosed as a result of standard-of-care (SOC) screening in the US. MCED tests may expand screening to more cancers, but the long-term outcomes of MCED test-detected cancers are unknown. DETECT-A was the first large prospective interventional clinical trial to evaluate an MCED blood test. The test used was an early version of CancerSEEK and was evaluated in 9,911 women without history of cancer ( Science 369:6499, 2020). CancerSEEK, coupled with diagnostic PET-CT, safely identified cancers including those not detected by SOC screening, the majority of which were localized or regional. This follow-up observational study evaluated longitudinal clinical outcomes of cancers diagnosed as a result of an abnormal CancerSEEK test with a median follow up of 4.4 (IQR:4.1-4.6) years from initial CancerSEEK testing. Methods: Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnosis, treatment, treatment response, remission status, recurrence, secondary cancer diagnoses, and mortality (cancer-related and all-cause) was extracted from electronic medical records through November 2022. Data collection for living participants took place a median of 3.7 years following cancer diagnosis (IQR: 3.3-3.9) and a median of 4.3 years (IQR: 4.1-4.7) following initial CancerSEEK screen. Results: Fourteen (53.8%) participants underwent surgery; 5 had surgery alone, 9 had surgery with adjuvant and/or neoadjuvant chemotherapy, radiation, or hormone therapy. Twelve of 14 (85.7%) surgically treated participants were in remission as of November 2022, including 10 with localized or regional disease at diagnosis. Among patients whose treatment was non-surgical (11) or unknown (1), 1 (8.3%) was in remission (stage I at diagnosis), 9 (75.0%) were deceased (all stage III or IV at diagnosis), and 2 (16.7%) were in surveillance or ongoing treatment (stage II and stage III at diagnosis). Overall, 13 of 26 (50%) participants were in remission [ovarian (4), thyroid (1), uterus (2), breast (1), colorectal (2), and lung (3)] ; 7 of these 13 (54%) had cancers without recommended SOC screening modalities. Eleven of 17 (64.7%) participants with localized or regional disease (stage I, II, or III) were in remission, whereas 2 of 9 (22.2%) with stage IV disease at diagnosis were in remission. Conclusions: CancerSEEK detected cancers earlier in patients who, when treated subsequently with conventional methods, achieved long-term survival. Half of all patients with a CancerSEEK-detected cancer remain cancer-free after treatment 〉 4 years (median) after their initial CancerSEEK test. This includes 7 patients with cancer types for which no SOC screening option exists. Additional biomarkers, new analytic methods and algorithms are being incorporated in the development of the next generation of the MCED test.
    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
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 38 ( 2017-09-19), p. 10202-10207
    Abstract: The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer. KRAS mutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient’s primary tumor (100% concordance). The use of KRAS in conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
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  • 4
    In: Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 11, No. 501 ( 2019-07-17)
    Abstract: Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.
    Type of Medium: Online Resource
    ISSN: 1946-6234 , 1946-6242
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
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  • 5
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 359, No. 6378 ( 2018-02-23), p. 926-930
    Abstract: Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 3039-3039
    Abstract: 3039 Background: Recommended standard of care (SOC) early detection tests are solely available for four cancer types and fewer than 20% of incident cancers in the US are being diagnosed as a result of screening. Advances in detection of tumor-derived analytes in the blood are enabling the development of MCED tests that may expand early cancer detection. While MCED tests are being designed with high specificity, false positive (FP) results remain a concern for clinicians and patients alike, as no long-term outcomes of individuals with a FP MCED test have been reported. DETECT-A was the first prospective interventional clinical trial to evaluate an MCED blood test. The test used was an early version of CancerSEEK, evaluated in 9,911 women without history of cancer ( Science, 369:6499, 2020). This prospectively planned analysis evaluates cancer incidence among DETECT-A participants with FP results, with the intention of providing key long-term data on test effectiveness. Methods: This analysis included 98 DETECT-A participants with FP results, where a FP was defined as a positive CancerSEEK result with subsequent PET-CT and clinical evaluation with no evidence of cancer within 1 year of the initial CancerSEEK test. Sixty-three of 98 participants had no follow-up procedure performed after imaging, and 35 subjects had noninvasive/minimally invasive follow-up procedures performed. Electronic medical records were analyzed from January 2020 through November 2022 for cancer diagnosis, treatment, remission, recurrence, and mortality. Results: Ninety-six of 98 participants with a FP result remained free of cancer with a median follow-up of 4.3 years (IQR: 3.9-4.9) from the initial CancerSEEK test. One stage I breast cancer and one stage III ovarian cancer were diagnosed 2.7 and 2.9 years respectively from the initial CancerSEEK test. Conclusions: Patients with a negative PET-CT and initial clinical evaluation after a positive CancerSEEK test had low ( 〈 1% per year) risk for cancer in the ensuing four years after the initial CancerSEEK test. If confirmed, this result should prove reassuring to clinicians and to patients who have no evidence of cancer on comprehensive imaging following a positive MCED test. Further, these results provide preliminary support for the recommendation that patients who participate in MCED testing and receive a FP result can safely return to routine care after comprehensive anatomic and functional imaging and clinical evaluation reveal no suspicion of cancer.
    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
    Location Call Number Limitation Availability
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