| 1. |
- Abbasi, Rasha, et al.
(författare)
-
IceCube search for neutrinos from GRB 221009A
- 2023
-
Ingår i: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
-
Konferensbidrag (refereegranskat)abstract
- GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
|
|
| 2. |
- Sclafani, Francesco, et al.
(författare)
-
Analysis of KRAS, NRAS, BRAF, PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients
- 2020
-
Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 146:1, s. 94-102
-
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.
|
|
| 3. |
- Sclafani, Francesco, et al.
(författare)
-
Comparison between MRI and pathology in the assessment of tumour regression grade in rectal cancer
- 2017
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 117:10, s. 1478-1485
-
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.
|
|
| 4. |
- Sclafani, Francesco, et al.
(författare)
-
FC gamma RIIa and FC gamma RIIa polymorphisms (SNPs) and cetuximab (C) benefit in the EXPERT-C trial
- 2014
-
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
-
Tidskriftsartikel (refereegranskat)
|
|
| 5. |
- Sclafani, Francesco, et al.
(författare)
-
Fc gamma RIIa and Fc gamma RIIIa Polymorphisms and Cetuximab Benefit in the Microscopic Disease
- 2014
-
Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 20:17, s. 4511-4519
-
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.
|
|
| 6. |
- Sclafani, Francesco, et al.
(författare)
-
KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
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.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
