Publications by authors named "B Pellegrino"

57 Publications

Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification.

Cancer Res 2022 04;82(8):1646-1657

Department of Medical Oncology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.

PARP inhibitors (PARPi) are approved drugs for platinum-sensitive, high-grade serous ovarian cancer (HGSOC) and for breast, prostate, and pancreatic cancers (PaC) harboring genetic alterations impairing homologous recombination repair (HRR). Detection of nuclear RAD51 foci in tumor cells is a marker of HRR functionality, and we previously established a test to detect RAD51 nuclear foci. Here, we aimed to validate the RAD51 score cut off and compare the performance of this test to other HRR deficiency (HRD) detection methods. Laboratory models from BRCA1/BRCA2-associated breast cancer, HGSOC, and PaC were developed and evaluated for their response to PARPi and cisplatin. HRD in these models and patient samples was evaluated by DNA sequencing of HRR genes, genomic HRD tests, and RAD51 foci detection. We established patient-derived xenograft models from breast cancer (n = 103), HGSOC (n = 4), and PaC (n = 2) that recapitulated patient HRD status and treatment response. The RAD51 test showed higher accuracy than HRR gene mutations and genomic HRD analysis for predicting PARPi response (95%, 67%, and 71%, respectively). RAD51 detection captured dynamic changes in HRR status upon acquisition of PARPi resistance. The accuracy of the RAD51 test was similar to HRR gene mutations for predicting platinum response. The predefined RAD51 score cut off was validated, and the high predictive value of the RAD51 test in preclinical models was confirmed. These results collectively support pursuing clinical assessment of the RAD51 test in patient samples from randomized trials testing PARPi or platinum-based therapies.

Significance: This work demonstrates the high accuracy of a histopathology-based test based on the detection of RAD51 nuclear foci in predicting response to PARPi and cisplatin.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-2409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612637PMC
April 2022

Varicella post-exposure management for pediatric oncology patients.

Bull Cancer 2022 Mar 31;109(3):287-295. Epub 2022 Jan 31.

The Hospital for Sick Children, Division of Hematology, Oncology, Department of Pediatrics, 555, University Avenue, Toronto, Canada. Electronic address:

Introduction: The objective was to evaluate health care providers' (HCP) adherence to and efficacy of varicella post-exposure prophylaxis (PEP) recommendations. It was an observational, prospective, multicenter study set in Ile-de-France, France.

Methods: All children under 18 with a cancer diagnosis, currently or within 3months of receiving cancer treatment, regardless of varicella zoster virus (VZV) serostatus or previous personal history of varicella, were eligible. Study participants with significant exposure were reviewed prospectively for PEP indications. Main outcome measures were the percentage of exposure situations for which HCP were guideline-compliant, the proportion of available VZV serostatuses and the incidence of breakthrough varicella after different PEP approaches.

Results: A total of 51 patients from 15 centers were enrolled after 52 exposure episodes. Median age at exposure was 5 years (range, 1-15). Exposure within the household led to 38% of episodes. Prophylactic treatment consisted in specific anti-VZV immunoglobulins (V-ZIG) (n=19) or in oral aciclovir (n=15). No prophylactic treatment was given for 18 patients (in compliance, n=16). In compliance with guidelines, 17 patients received V-ZIG, 11 did not develop varicella (65%, [95% CI, 39-90%]); 15 received aciclovir, 13 did not develop varicella (87%, [95% CI, 67-100%]). Breakthrough varicella occurred in 11 patients, with simple clinical course in all cases; in 8/47 (17%) episodes when PEP was guideline-compliant versus 3/5 (60%) when not.

Discussion: Recommendations have been respected and are efficient. PEP needs to be standardized and a study carried out to define the optimal approach. Anti-VZV immunization of seronegative family members should be encouraged.
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http://dx.doi.org/10.1016/j.bulcan.2021.11.016DOI Listing
March 2022

11 ESMO 2021 breakthroughs: practicing oncologist's perceptions on data presentation.

ESMO Open 2022 02 17;7(1):100376. Epub 2022 Jan 17.

Department of Medical Oncology, GZA Hospitals, Wilrijk, Belgium.

Background: The European Society for Medical Oncology (ESMO) 2021 conference provided a high number of randomized phase III trial reports, many of which were claimed to be practice changing. Given the short time available for conference presentations, results and conclusions tend to have greatest priority with less time remaining for study background and study methodology.

Purpose: On behalf of the ESMO Practicing Oncologists Working Group, 11 potentially practice-changing reports were selected and screened for three main questions: (i) Did the investigators provide sufficient details with regard to Patients and Methods to make the results comprehensible? (ii) Were there any reasons to consider bias? (iii) To which extent did the results presented translate to clinical benefit?

Results: In 2 out of 11 trials, the study design presented differed considerably from the study design described at ClinicalTrials.gov. Allocation concealment was not carried out in 6 out of 11 trials. In none of the trials reporting progression-free survival was informative censoring considered an issue. In none of the trials reporting overall survival was desirable crossover considered an issue. Defined trial outcome measures depicted at ClinicalTrials.gov, which could boost or weaken the ESMO-Magnitude of Clinical Benefit Scale score, were often lacking in the presentation. Study success was claimed in a heterogeneous manner, which was often not clearly linked to overall clinical benefit.

Conclusion: ESMO conference presentations can inform the scientific community and catalyze further research but cannot replace the full papers in peer-reviewed journals, which are needed to estimate the thoroughness of the results, the overall impact on clinical benefit and the consequences for future treatment guidelines.
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http://dx.doi.org/10.1016/j.esmoop.2021.100376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783088PMC
February 2022

Prevalence of ANCA-associated vasculitis amid natural gas drilling sites in West Virginia.

J Nephrol 2022 May 6;35(4):1185-1192. Epub 2022 Jan 6.

Department of Medicine, Section of Nephrology, West Virginia University School of Medicine, Morgantown, WV, USA.

Background: The epidemiology of ANCA-associated vasculitis (AAV) varies by ethnicity and region. Environmental exposure has been implicated in the pathophysiology of MPO-AAV. The aim of this study was to evaluate the epidemiology of AAV and explore a potential relationship with environmental factors in north central West Virginia.

Methods: This is a retrospective cohort study of 212 patients diagnosed with AAV at West Virginia University and its affiliated hospitals from January 1, 1990 to December 31, 2019. We assessed prevalence of AAV over time according to patient's zip codes and counties. Silica exposure through natural gas extraction was considered as a possible environmental factor.

Results: The proportion of patients with MPO-ANCA increased after 2010 (37.5% before 2010 vs 61% after 2010, p = 0.008). At the same time, the prevalence of AAV in Monongalia and surrounding counties has increased significantly after 2010 from 64.8 to 141.9 cases per million (p = 0.001). The increase in prevalence of AAV was primarily due to an increase in MPO-AAV (43 vs 101.7 cases per million before and after 2010, respectively, p = 0.028). During this time, the production of natural gas through fracking increased, rising more than tenfold after 2010 (p-value < 0.001). Heat mapping reveals that the increase in cases of AAV occurred in areas of increased fracking activity.

Conclusions: There was an increase in the prevalence of patients who were newly diagnosed with AAV over time in north central West Virginia. Further studies are required to ascertain the potential role of environmental exposure in the pathophysiology of AAV.
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http://dx.doi.org/10.1007/s40620-021-01243-3DOI Listing
May 2022

The future potential of genome-wide mutational profiles in HRD detection in breast cancer.

Expert Rev Mol Diagn 2022 01 20;22(1):1-3. Epub 2021 Dec 20.

Department of Medicine and Surgery, University of Parma, Parma, Italy.

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http://dx.doi.org/10.1080/14737159.2022.2015328DOI Listing
January 2022
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