| 501. |
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| 502. |
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| 503. |
- Sundín, Anders, et al.
(författare)
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Contrast-enhanced CT scanning in vivo for the quantification of hepatic metastases from a human colonic cancer in the nude rat
- 1992
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 18:6, s. 615-623
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic metastases were induced in nude rats by intraportal injection of 2.5-5.0 x 10(6) cells from the human colonic cancer cell line LS 174 T. Quantification of tumour burden, expressed as relative metastatic area, was performed by contrast-enhanced computed tomography (CT) scanning in vivo (n = 14), contrast enhanced CT scanning post mortem (n = 21) and computer-based area calculation (CBAC) (n = 21). To determine the false-positive contribution to the estimated tumour burden by the evaluation procedures themselves, six rats without metastases were assessed. The quantification in the three different assessment groups was in close accordance in animals with an intermediate or extensive metastatic burden, but not in rats with a minor (< 4%) tumour burden. The results indicate that contrast-enhanced CT scanning can be used in this model to quantify hepatic metastases, except in animals with few and small lesions. Furthermore, the results suggest a potential for the assessment of therapeutic response by repeated contrast-enhanced CT scanning in vivo, as well as prospects for a corresponding evaluation in man.
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| 504. |
- Sundín, Anders, et al.
(författare)
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Radioimmunolocalization of hepatic metastases and subcutaneous xenografts from a human colonic cancer in the nude rat : Aspects of tumour implantation site and mode of antibody administration
- 1993
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 32:7-8, s. 877-885
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Tidskriftsartikel (refereegranskat)abstract
- Antibody localization was analyzed following intraperitoneal (i.p.) or intravenous (i.v.) injection of the 125I-labelled anti-CEA-MAb I-38S1 in 44 nude rats, in order to evaluate the influence of tumour implantation site and the route of MAb administration. The animals were xenografted with a human colonic cancer (LS 174 T), either in the form of hepatic metastases, subcutaneous (s.c.) tumours or both. Tissue measurements, 4 days after MAb injection, showed better uptake for hepatic than for s.c. tumours, irrespective of the route of antibody administration. Antibody accumulation per g liver metastases was not size dependent for noduli weighing between 4 and 1,110 mg. MAb excretion evaluated in 20 animals and blood activity studied in 11 rats were equivalent 24-96 h following i.p. and i.v. injection. Dissimilar autoradiographic patterns were seen in hepatic metastases with predominantly peripherally located clusters following i.p. and more homogeneously distributed grains after i.v. MAb administration. The results indicate that tumour implantation site has a quantitative, and the route of administration at least a qualitative impact on the tumour accretion of anti-CEA MAb I-38S1 in the present xenograft model.
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| 505. |
- Sundström, Magnus, et al.
(författare)
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KRAS analysis in colorectal carcinoma : analytical aspects of Pyrosequencing and allele-specific PCR in clinical practice
- 2010
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10, s. 660-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidermal growth factor receptor inhibitor therapy is now approved for treatment of metastatic colorectal carcinomas (CRC) in patients with tumors lacking KRAS mutations. Several procedures to detect KRAS mutations have been developed. However, the analytical sensitivity and specificity of these assays on routine clinical samples are not yet fully characterised.Methods: The practical aspects and clinical applicability of a KRAS-assay based on Pyrosequencing were evaluated in a series of 314 consecutive CRC cases submitted for diagnostic KRAS analysis. The performance of Pyrosequencing compared to allele-specific, real-time PCR was then explored by a direct comparison of CE-IVD-marked versions of Pyrosequencing and TheraScreen (DxS) KRAS assays for a consecutive subset (n = 100) of the 314 clinical CRC samples.Results: Using Pyrosequencing, 39% of the 314 CRC samples were found KRAS-mutated and several of the mutations (8%) were located in codon 61. To explore the analytical sensitivity of the Pyrosequencing assay, mutated patient DNA was serially diluted with wild-type patient DNA. Dilutions corresponding to 1.25-2.5% tumor cells still revealed detectable mutation signals. In clinical practice, our algorithm for KRAS analysis includes a reanalysis of samples with low tumor cell content (< 10%, n = 56) using an independent assay (allele-specific PCR, DxS). All mutations identified by Pyrosequencing were then confirmed and, in addition, one more mutated sample was identified in this subset of 56 samples. Finally, a direct comparison of the two technologies was done by re-analysis of a subset (n = 100) of the clinical samples using CE-IVD-marked versions of Pyrosequencing and TheraScreen KRAS assays in a single blinded fashion. The number of samples for which the KRAS codon 12/13 mutation status could be defined using the Pyrosequencing or the TheraScreen assay was 94 and 91, respectively, and both assays detected the same number of codon 12 and 13 mutations.Conclusions: KRAS mutation detection using Pyrosequencing was evaluated on a consecutive set of clinical CRC samples. Pyrosequencing provided sufficient analytical sensitivity and specificity to assess the mutation status in routine formalin-fixed CRC samples, even in tissues with a low tumor cell content.
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| 506. |
- Suzuki, Chikako, et al.
(författare)
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Impact of the first tumor response at eight weeks on overall survival in metastatic breast cancer patients treated with first-line combination chemotherapy
- 2013
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Ingår i: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this was to determine whether the change of size observed at the first response evaluation after initiation of first-line combination chemotherapy correlates with overall survival (OS) in patients with metastatic breast cancer (MBC). The change in size of tumors derived from measurements according to Response Evaluation Criteria In Solid Tumors (RECIST) at the first evaluation on computed tomography (CT) was obtained from a multicenter, randomized phase III trial ("TEX trial," n = 287) comparing treatment with a combination of epirubicin and paclitaxel alone or with capecitabine (TEX). Cox regression and Kaplan-Meier analyses were performed to evaluate the correlations between the first change in tumor size, response according to RECIST and OS. Data from CT evaluations of 233 patients were available. Appearance of new lesions or progression of non-target lesions (new/non-target) indicated short OS by univariable regression analysis (HR 3.76, 95 % CI 1.90-7.42, p andlt; 0.001). A decrease by andgt;30 % at this early time point was prognostic favorable (HR 0.69, 95 % CI 0.49-0.98, p = 0.04) and not significantly less than the best overall response according to RECIST. After adjustment for previous adjuvant treatment and the treatment given within the frame of the randomized trial, OS was still significantly shorter in patients with new/non-target lesions after a median 8 weeks of treatment (HR 4.41, 95 % CI 2.74-7.11, p andlt; 0.001). Disease progression at the first evaluation correlates with OS in patients with MBC treated with first-line combination chemotherapy. The main reason for early disease progression was the appearance of new lesions or progression of non-target lesions. These patients had poor OS even though more lines of treatment were available. Thus, these factors should be focused on in the response evaluations besides tumor size changes.
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| 507. |
- Suzuki, C, et al.
(författare)
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The initial change in tumor size predicts response and survival in patients with metastatic colorectal cancer treated with combination chemotherapy
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 23:4, s. 948-954
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To determine whether the change in tumor diameters at the first follow-up computed tomography (CT) examination after baseline examination (first change) correlates with outcome in patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.PATIENTS AND METHODS: The first change was analyzed in a multicenter randomized phase III trial (Nordic VI, N = 567) comparing first-line irinotecan with either bolus or infused 5-fluorouracil. Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses after correction for guarantee-time bias were carried out to evaluate correlations between first change, objective response according to RECIST 1.0, progression-free survival (PFS), and overall survival (OS).RESULTS: The hazard ratios for PFS and OS decreased along with first change. A decrease between 10% and <30%, albeit RECIST does not regard this as a partial response, was a positive prognostic factor for PFS and OS. Patients who had new lesions or unequivocal progression of nonmeasurable lesions had a worse prognosis than those with only an increase in size of >20%.CONCLUSIONS: The change in tumor size at the first follow-up CT is strongly prognostic for PFS and OS in mCRC.
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| 508. |
- Syk, Erik, et al.
(författare)
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Factors influencing local failure in rectal cancer : analysis of 2315 patients from a population-based series
- 2010
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Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 53:5, s. 744-752
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study aimed to identify risk factors for local failure in an effort to optimize treatment for rectal cancer. METHODS: A total of 154 patients with local failure after abdominal resection were identified from a population-based consecutive series of 2315 patients who underwent operations for rectal cancer in the Stockholm region between January 1995 and December 2004. Surgeons trained in total mesorectal excision performed the surgery, and preoperative radiotherapy was given according to defined protocols. Data from the 9 hospitals in the region, prospectively registered in a database, were reviewed with regard to tumor location and stage, radiation therapy, surgical treatment, and follow-up. RESULTS: In a multivariable analysis, independent risk factors for local failure were distal tumor location and advanced tumor and nodal stage, omission of preoperative radiation, residual disease, and hospitals with lower caseload. Low anterior resection and total mesorectal excision were deployed more often in centers with low failure rates. Discriminators for radiation therapy were patients with male gender, less advanced age, and tumors situated <6 cm from the anal verge. CONCLUSION: The variability of patient outcome according to local failure depends on tumor stage, nodal stage, and location. Omission of radiation therapy and surgical performance are important additional risk factors to consider when optimizing treatment for rectal cancer.
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| 509. |
- Syk, Erik, et al.
(författare)
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Local recurrence in rectal cancer : anatomic localization and effect on radiation target
- 2008
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 72:3, s. 658-64
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine the sites of local recurrence after total mesorectal excision for rectal cancer in an effort to optimize the radiation target. METHODS AND MATERIALS: A total of 155 patients with recurrence after abdominal resection for rectal cancer were identified from a population-based consecutive cohort of 2,315 patients who had undergone surgery by surgeons trained in the total mesorectal excision procedure. A total of 99 cross-sectional imaging studies were retrieved and re-examined by one radiologist. The clinical records were examined for the remaining patients. RESULTS: Evidence of residual mesorectal fat was identified in 50 of the 99 patients. In 83 patients, local recurrence was identified on the imaging studies. All recurrences were within the irradiated volume if the patients had undergone preoperative radiotherapy or within the same volume if they had not. The site of recurrence was in the lower 75% of the pelvis, anatomically below the S1-S2 interspace for all patients. Only 5 of the 44 recurrences in patients with primary tumors >5 cm from the anal verge were in the lowest 20% of the pelvis. Six recurrences involved the lateral lymph nodes. CONCLUSION: These data suggest that a lowering of the upper limit of the clinical target volume could be introduced. The anal sphincter complex with surrounding tissue could also be excluded in patients with primary tumors >5 cm from the anal verge.
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| 510. |
- Syk, Erik, et al.
(författare)
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Radiological findings do not support lateral residual tumour as a major cause of local recurrence of rectal cancer
- 2006
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Ingår i: British Journal of Surgery. - West Sussex, United Kingdom : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 93:1, s. 113-119
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: The aim of this study was to determine the sites of local recurrence following radical (R0) total mesorectal excision (TME) for rectal cancer in an effort to elucidate the reasons for recurrence. METHODS: Thirty-seven patients with recurrence following curative resection for rectal cancer were identified from a population of 880 patients operated on by surgeons trained in the TME procedure. Two radiologists independently examined 33 available computed tomograms and magnetic resonance images taken when the recurrence was detected. RESULTS: Twenty-nine of the 33 recurrences were found in the lower two-thirds of the pelvis. Two recurrent tumours appeared to originate from lateral pelvic lymph nodes. Evidence of residual mesorectal fat was identified in 15 patients. Fourteen of the recurrent tumours originated from primary tumours in the upper rectum; all of these tumours recurred at the anastomosis and 12 of the 14 patients had evidence of residual mesorectal fat. CONCLUSION: Lateral pelvic lymph node metastases are not a major cause of local recurrence after TME. Partial mesorectal excision may be associated with an increased risk of local recurrence from tumours in the upper rectum.
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