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- Bratulic, Sinisa, 1981, et al.
(författare)
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Noninvasive detection of any-stage cancer using free glycosaminoglycans.
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:50
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Tidskriftsartikel (refereegranskat)abstract
- Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine and plasma free glycosaminoglycan profiles (GAGomes) as tumor metabolism biomarkers for multi-cancer early detection (MCED) of 14 cancer types using 2,064 samples from 1,260 cancer or healthy subjects. We observed widespread cancer-specific changes in biofluidic GAGomes recapitulated in an in vivo cancer progression model. We developed three machine learning models based on urine (Nurine = 220 cancer vs. 360 healthy) and plasma (Nplasma = 517 vs. 425) GAGomes that can detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 with up to 62% sensitivity to stage I disease at 95% specificity. Undetected patients had a 39 to 50% lower risk of death. GAGomes predicted the putative cancer location with 89% accuracy. In a validation study on a screening-like population requiring ≥ 99% specificity, combined GAGomes predicted any cancer type with poor prognosis within 18 months with 43% sensitivity (21% in stage I; N = 121 and 49 cases). Overall, GAGomes appeared to be powerful MCED metabolic biomarkers, potentially doubling the number of stage I cancers detectable using genomic biomarkers.
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| 2. |
- Nyman, Jan, 1956, et al.
(författare)
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Accelerated hyperfractionated radiotherapy combined with induction and concomitant chemotherapy for inoperable non-small-cell lung cancer--impact of total treatment time.
- 1998
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Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X .- 1651-226X. ; 37:6, s. 539-45
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Tidskriftsartikel (refereegranskat)abstract
- Tumour cell proliferation during conventionally fractionated radiotherapy (RT) can negatively influence the treatment outcome in patients with unresectable non-small-cell lung cancer (NSCLC). Accelerated and hyperfractionated RT may therefore have an advantage over conventional RT. Moreover, earlier studies have suggested improved survival with addition of cisplatin-based chemotherapy (CT). We present here the results of combined treatment with induction and concomitant CT and accelerated hyperfractionated RT in a retrospective series of patients with advanced NSCLC. Between August 1990 and August 1995, 90 consecutive patients, aged 42-77 years (median 63 years), with locally advanced unresectable or medically inoperable NSCLC and good performance status were referred for treatment: stage: I 23%, IIIa 37%, IIIb 40%. Patient histologies included: squamous cell carcinoma 52%, adenocarcinoma 34% and large cell carcinoma 13%. The treatment consisted of two courses of CT (cisplatin 100 mg/m2 day 1 and etoposide 100 mg/m2 day 1-3 i.v.), the second course given concomitantly with RT. The total RT dose was 61.2-64.6 Gy, with two daily fractions of 1.7 Gy. A one-week interval was introduced after 40.8 Gy to reduce acute toxicity, making the total treatment time 4.5 weeks. Concerning toxicity, 33 patients had febrile neutropenia, 10 patients suffered from grade III oesophagitis and 7 patients had grade III pneumonitis. There were two possible treatment-related deaths, one due to myocardial infarction and the other due to a pneumocystis carinii infection. The 1-, 2- and 3-year overall survival rates were 72%, 46% and 34%, respectively; median survival was 21.3 months. Fifty-nine patients had progressive disease: 21 failed locoregionally, 29 had distant metastases and 9 patients had a combination of these. Pretreatment weight loss was the only prognostic factor found, except for stage. However, the results for stage IIIb were no different from those for stage IIIa. We conclude that the survival results compare favourably with those of most other studies with a manageable toxicity.
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