| 481. |
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| 482. |
- Schöllkopf, Claudia, et al.
(författare)
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Cigarette smoking and risk of non-Hodgkin's lymphoma : a population-based case-control study
- 2005
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 14:7, s. 1791-1796
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiologic evidence of an association between tobacco smoking and non-Hodgkin's lymphoma has been conflicting. This may reflect that non-Hodgkin's lymphoma comprises several distinct disease entities with different etiologies, as some studies have indicated an association between smoking and follicular lymphoma. OBJECTIVE: To investigate the association between cigarette smoking and non-Hodgkin's lymphoma risk, overall and by subtype. METHODS: As part of a nationwide Danish-Swedish population-based case-control study, we interviewed 3,055 incident non-Hodgkin's lymphoma patients and 3,187 population controls. All lymphomas were uniformly classified according to the WHO classification. We used unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for the association between cigarette smoking and risk of non-Hodgkin's lymphoma. RESULTS: Cigarette smoking was not associated with the risk of non-Hodgkin's lymphoma overall (OR, 0.97; 95% CI, 0.87-1.08) nor with the major subgroups such as diffuse large B-cell lymphoma (OR, 0.94; 95% CI, 0.79-1.10), chronic lymphocytic leukemia (OR, 0.86; 95% CI, 0.72-1.02), or follicular lymphoma (OR, 1.03; 95% CI, 0.85-1.24). Female smokers were at a marginally increased risk of follicular lymphoma (OR, 1.41; 95% CI, 1.04-1.92). Men who had ever smoked had a significantly increased risk of T-cell lymphoma (OR, 1.67; 95% CI, 1.11-2.51). No dose-response association with cigarette smoking could be established for any lymphoma subgroup. CONCLUSION: We found little evidence of an association between cigarette smoking and non-Hodgkin's lymphoma risk overall. Although increased risks of follicular lymphoma in female smokers and of T-cell lymphoma in male smokers were suggested, no dose-response relationship was observed, leaving limited support for causality.
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| 483. |
- Schöllkopf, Claudia, et al.
(författare)
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Hepatitis C infection and risk of malignant lymphoma
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 122:8, s. 1885-1890
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Tidskriftsartikel (refereegranskat)abstract
- The association between hepatitis C virus (HCV) infection and risk of malignant lymphoma remains controversial, perhaps due to small-sized studies and low prevalence of HCV in the general population. On the basis of a large Danish-Swedish population-based case-control study, 2,819 lymphoma patients and 1,856 controls of second-generation Danish-Swedish origin were screened for HCV infection using an enzyme-linked immunosorbent assay and a confirming recombinant immunoblot assay (RIBA) test. Positive samples were tested with real-time PCR for the presence of HCV RNA. The association between HCV infection and risk of malignant lymphoma was assessed by logistic regression. When intermediate RIBA test results were interpreted as positive, anti-HCV antibody positivity was associated with a nonsignificant increased risk of non-Hodgkin lymphoma (NHL) overall (odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.9-5.3; n = 20 cases), of B-cell lymphomas combined (OR = 2.4 [1.0-5.8]; n = 20) and of lymphoplasmacytic lymphoma (OR = 5.2 [1.0-26.4]; n = 2). No patients with T-cell or Hodgkin lymphoma were HCV-positive. A more conservative definition of HCV positivity (disregarding intermediate RIBA results) resulted in an OR = 1.6 (0.3-8.5; n = 5) for NHL overall. When the definition was further restricted to require HCV RNA positivity, OR was 1.7 (0.2-16.2; n = 3) for NHL overall. Our findings from a population with a low prevalence of HCV suggest a positive association between HCV and risk of NHL, in particular of B-cell origin.
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| 484. |
- Sclafani, Francesco, et al.
(författare)
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Analysis of KRAS, NRAS, BRAF, PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients
- 2020
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 146:1, s. 94-102
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Tidskriftsartikel (refereegranskat)abstract
- Little information is available on the clinical significance of cancer-related genes such as KRAS, NRAS, BRAF, PIK3CA and TP53 in nonmetastatic rectal cancer. We investigated mutations of these genes in a large prospective series of locally advanced rectal cancer (LARC) patients who were recruited into two phase II trials. Mutational analyses were performed with diagnostically validated methods including polymerase chain reaction, capillary electrophoresis single-strand conformational analysis, Sanger sequencing and next-generation sequencing. Associations between single or multiple gene mutations and clinicopathological characteristics and treatment outcomes were explored. Of these 269, 210 (78%) patients were assessable. Mutations of KRAS, NRAS, BRAF, PIK3CA and TP53 occurred in 43, 9, 4, 9 and 60% of patients, respectively. Concordance between paired biopsy and resection specimens was 82% for KRAS, 95% for NRAS, 99% for BRAF, 96% for PIK3CA and 63% for TP53. TP53 mutations were associated with extramural venous invasion on baseline MRI (78% vs. 65%, p = 0.04), poor pathological tumour regression (23% vs. 36%, p = 0.05) and a trend toward a worse 5-year progression-free survival (PFS; 60% vs. 74%, HR 1.59, p = 0.06). Patients with tumours harbouring mutation of TP53 and either KRAS or NRAS (32%) had a worse 5-year PFS than those with TP53/KRAS/NRAS wild-type tumours (54% vs. 72%, HR 1.75, p = 0.02). In univariate analysis, BRAF mutation predicted poor 5-year overall survival only among patients treated without cetuximab (20% vs. 73%, HR 3.29, p = 0.03). This is one of the largest biomarker studies in a prospective, largely homogeneous, LARC population. Our findings are hypothesis generating and require validation in independent series.
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| 485. |
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| 486. |
- Sclafani, Francesco, et al.
(författare)
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Comparison between MRI and pathology in the assessment of tumour regression grade in rectal cancer
- 2017
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 117:10, s. 1478-1485
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Tidskriftsartikel (refereegranskat)abstract
- Background: Limited data exist regarding the correlation between MRI tumour regression grade (mrTRG) and pathological TRG (pTRG) in rectal cancer. Methods: mrTRG and pTRG were compared in rectal cancer patients from two phase II trials (EXPERT and EXPERT-C). The agreement between radiologist and pathologist was assessed with the weighted k test while the Kaplan-Meier method was used to estimate survival outcomes. Results: One hundred ninety-one patients were included. Median time from completion of neoadjuvant treatment to pre-operative MRI and surgery was 4.1 weeks (interquartile range (IQR): 3.7-4.7) and 6.6 weeks (IQR: 5.9-7.6), respectively. Fair agreement was found between mrTRG and pTRG when regression was classified according to standard five-tier systems (kappa = 0.24) or modified three-tier systems (kappa = 0.25). Sensitivity and specificity of mrTRG 1-2 (complete/good radiological regression) for the prediction of pathological complete response was 74.4% (95% CI: 58.8-86.5) and 62.8% (95% CI: 54.5-70.6), respectively. Survival outcomes of patients with intermediate pathological regression (pTRG 2) were numerically better if complete/good regression was also observed on imaging (mrTRG 1-2) compared to poor regression (mrTRG 3-5) (5-year recurrence-free survival 76.9% vs 65.9%, P = 0.18; 5-year overall survival 80.6% vs 68.8%, P = 0.22). Conclusions: The agreement between mrTRG and pTRG is low and mrTRG cannot be used as a surrogate of pTRG. Further studies are warranted to assess the ability of mrTRG to identify pathological complete responders for the adoption of non-operative management strategies and to provide complementary prognostic information to pTRG for better risk-stratification after surgery.
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| 487. |
- Sclafani, Francesco, et al.
(författare)
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FC gamma RIIa and FC gamma RIIa polymorphisms (SNPs) and cetuximab (C) benefit in the EXPERT-C trial
- 2014
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Ingår i: Journal of Clinical Oncology. - Royal Marsden NHS Fdn Trust, London, England. Royal Marsden NHS Fdn Trust, Surrey, England. Vall Hebren Univ Hosp, Barcelona, Spain. Akad Univ Hosp, Uppsala, Sweden. Univ Valencia, INCLIVA, Dept Hematol & Med Oncol, Valencia, Spain.. - 0732-183X .- 1527-7755. ; 32:15
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Tidskriftsartikel (refereegranskat)
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| 488. |
- Sclafani, Francesco, et al.
(författare)
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Fc gamma RIIa and Fc gamma RIIIa Polymorphisms and Cetuximab Benefit in the Microscopic Disease
- 2014
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 20:17, s. 4511-4519
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Fc gamma R polymorphisms have been reported to enhance the immune-mediated effects of cetuximab in metastatic colorectal cancer. There are no data on the relationship between these polymorphisms and cetuximab in the early-stage setting. We performed a pharmacogenomic analysis of EXPERT-C, a randomized phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX +/- cetuximab in high-risk, locally advanced rectal cancer. Experimental Design: Fc gamma RIIa-H131R and Fc gamma RIIIa-V158F polymorphisms were analyzed on DNA from peripheral blood samples. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results: Genotyping was successfully performed in 105 of 164 (64%) patients (CAPOX = 54, CAPOX-C = 51). No deviation fromthe Hardy-Weinberg equilibrium or association of these polymorphisms with tumor RAS status was observed. Fc gamma RIIa-131R (HR, 0.38; P = 0.058) and Fc gamma RIIIa-158F alleles (HR, 0.21; P = 0.007) predicted improved progression-free survival (PFS) in patients treated with cetuximab. In the CAPOX-C arm, carriers of both 131R and 158F alleles had a statistically significant improvement in PFS (5 years: 78.4%; HR, 0.22; P = 0.002) and overall survival (OS; 5 years: 86.4%; HR, 0.24; P = 0.018) when compared with patients homozygous for 131H and/or 158V (5-year PFS: 35.7%; 5-year OS: 57.1%). An interaction between cetuximab benefit and 131R and 158F alleles was found for PFS (P = 0.017) and remained significant after adjusting for prognostic variables (P = 0.003). Conclusion: This is the first study investigating Fc gamma RIIa and Fc gamma RIIIa polymorphisms in patients with early-stage colorectal cancer treated with cetuximab. We showed an increased clinical benefit from cetuximab in the presence of 131R and 158F alleles.
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| 489. |
- Sclafani, F., et al.
(författare)
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HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab
- 2013
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:12, s. 3123-3128
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Tidskriftsartikel (refereegranskat)abstract
- HER2 is an established therapeutic target in breast and gastric cancers. The role of HER2 in rectal cancer is unclear, as conflicting data on the prevalence of HER2 expression in this disease have been reported. We evaluated the prevalence of HER2 and its impact on the outcome of high-risk rectal cancer patients treated with neoadjuvant CAPOX and CRT +/- cetuximab in the EXPERT-C trial. Eligible patients with available tumour tissue for HER2 analysis were included. HER2 expression was determined by immunohistochemistry (IHC) in pre-treatment biopsies and/or surgical specimens (score 0-3+). Immunostaining was scored according to the consensus panel recommendations on HER2 scoring for gastric cancer. Tumours with equivocal IHC result (2+) were tested for HER2 amplification by D-ISH. Tumours with IHC 3+ or D-ISH ratio >= 2.0 were classified as HER2+. The impact of HER2 on primary and secondary end points of the study was analysed. Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3 of 104 (2.9%) and 3 of 114 (2.6%) were HER2+, respectively. In 77 patients with paired specimens, concordance for HER2 status was found in 74 (96%). Overall, 141 patients were assessable for HER2 and 6 out of 141 (4.3%) had HER2 overexpression and/or amplification. The median follow-up was 58.6 months. HER2 was not associated with a difference in the outcome for any of the study end points, including in the subset of 90 KRAS/BRAF wild-type patients treated +/- cetuximab. Based on the low prevalence of expression as recorded in the EXPERT-C trial, HER2 does not appear to represent a useful therapeutic target in high-risk rectal cancer. However, the role of HER2 as a potential predictive biomarker of resistance to anti-EGFR-based treatments and a therapeutic target in anti-EGFR refractory metastatic colorectal cancer (CRC) warrants further investigation. Trial registration: ISRCTN Register: 99828560.
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| 490. |
- Sclafani, Francesco, et al.
(författare)
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KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- There are limited data on circulating, cell-free, tumour (ct) DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd) PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX +/- cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting.
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