Ramon-y-Cajal, T. (Teresa)
- Publications
- item.page.relationships.isContributorAdvisorOfPublication
- item.page.relationships.isContributorOfPublication
4 results
Search Results
Now showing 1 - 4 of 4
- Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC)(Oxford University Press, 2017) Grande, E. (Enrique); Zafón, C. (Carles); Porras, I. (Ignacio); Palacios, N. (Nuria); Matos, I. (Ignacio); Medina-Martínez, J. (Javier); Ramon-y-Cajal, T. (Teresa); González-Astorga, B. (Beatriz); Aller, J. (Javier); Trigo, J.M. (Jose Manuel); Manzano, J.L. (José Luis); García-Adrián, S. (Silvia); Cillán, E. (Elena); Duran-Poveda, M. (Manuel); Bohn, U. (Uriel); Reina, J.J. (Juan Jose); Reig, Ó. (Ó.); López-Alfonso, A. (Ana); Capdevila, J. (Jaume); Grau, J.J. (Juan Jose)Background Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012–November 2014). Subjects and Methods 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n = 34) or medullary thyroid cancer (MTC, n = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Results Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0–24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1–12.2) (DTC: 7.4 months (95% CI: 3.1–11.8) and MTC: 9.4 months (95% CI: 4.8–13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Conclusion Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies.
- Risk of cancer in family members of patients with lynch-like syndrome(MDPI AG, 2020) Cubiella, J. (Joaquin); Garau, C. (Catalina); López-Fernández, A. (Adrià); Sánchez, A. (Ariadna); Ramon-y-Cajal, T. (Teresa); Balaguer, F. (Francesc); Carrillo-Palau, M. (Marta); Alustiza, M. (Miren); Herraiz-Bayod, M.J. (Maite J.); López, M.J. (María Jesús); Castells, A. (Antoni); Giner-Calabuig, M. (Mar); Murcia, Ó. (Óscar); Picó, M.D. (María Dolores); Zapater, P. (Pedro); Yagüe, C. (Carmen); Llort, G. (Gemma); Bujanda, L. (Luis); Castillejo, A. (Adela); Jover, R. (Rodrigo); Sánchez‑Heras, A.B. (Ana Beatriz); Moreira, L. (Leticia); Rivas, L. (Laura); Pellise, M. (María); Gisbert-Beamud, A. (Alexandra); Salces, I. (Inmaculada); Lacueva, F.J. (Francisco Javier); Alenda, C. (Cristina); Soto, J.L. (José L.); Alvarez-Urturi, C. (Cristina)Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56–2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67–4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44–2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26–5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk.
- Clinical and Pathological Characterization of Lynch-Like Syndrome(AGA Institute, 2020) Picó, M.D. (María Dolores); Castillejo, A. (Adela); Murcia, Ó. (Óscar); Giner-Calabuig, M. (Mar); Alustiza, M. (Miren); Sánchez, A. (Ariadna); Moreira, L. (Leticia); Pellise, M. (María); Castells, A. (Antoni); Carrillo-Palau, M. (Marta); Ramon-y-Cajal, T. (Teresa); Gisbert-Beamud, A. (Alexandra); Llort, G. (Gemma); Yagüe, C. (Carmen); López-Fernández, A. (Adrià); Alvarez-Urturi, C. (Cristina); Cubiella, J. (Joaquin); Rivas, L. (Laura); Rodríguez-Alcalde, D. (Daniel); Herraiz, M. T. (María Teresa); Garau, C. (Catalina); Dolz, C. (Carlos); Bujanda, L. (Luis); Cid, L. (Lucia); Povés, C. (Carmen); Garzon, M. (Marta); Salces, I. (Inmaculada); Ponce, M. (Marta); Hernández-Villalba, L. (Luis); Alenda, C. (Cristina)Background & Aims Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins—this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS. We collected data from a large series of patients with LLS to identify clinical and pathology features. Methods We collected data from a nationwide-registry of patients with colorectal cancer (CRC) in Spain. We identified patients whose colorectal tumors had loss of MSH2, MSH6, PMS2, or MLH1 (based on immunohistochemistry), without the mutation encoding V600E in BRAF (detected by real-time PCR), and/or no methylation at MLH1 (determined by methylation-specific multiplex ligation-dependent probe amplification), and no pathogenic mutations in MMR genes, BRAF, or EPCAM (determined by DNA sequencing). These patients were considered to have LLS. We collected data on demographic, clinical, and pathology features and family history of neoplasms. The χ2 test was used to analyze the association between qualitative variables, followed by the Fisher exact test and the Student t test or the Mann-Whitney test for quantitative variables. Results We identified 160 patients with LLS; their mean age at diagnosis of CRC was 55 years and 66 patients were female (41%). The Amsterdam I and II criteria for Lynch syndrome were fulfilled by 11% of cases and the revised Bethesda guideline criteria by 65% of cases. Of the patients with LLS, 24% were identified in universal screening. There were no proportional differences in sex, indication for colonoscopy, immunohistochemistry, pathology findings, or personal history of CRC or other Lynch syndrome-related tumors between patients who met the Amsterdam and/or Bethesda criteria for Lynch syndrome and patients identified in universal screening for Lynch syndrome, without a family history of CRC. Conclusions Patients with LLS have homogeneous clinical, demographic, and pathology characteristics, regardless of family history of CRC.
- Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome(Elsevier, 2022) Sánchez, A. (Ariadna); Roos, V.H. (Victorine H.); Navarro, M. (Matilde); Pineda, M. (Marta); Caballol, B. (Berta); Moreno, L. (Lorena); Carballal, S. (Sabela); Rodríguez-Alonso, L. (Lorena); Ramon-y-Cajal, T. (Teresa); Llort, G. (Gemma); Piñol, V. (Virginia); López-Fernández, A. (Adrià); Salces, I. (Inmaculada); Picó, M.D. (María Dolores); Rivas, L. (Laura); Bujanda, L. (Luis); Garzon, M. (Marta); Pizarro, A. (Angeles); Martínez-de-Castro, E. (Eva); López-Arias, M.J. (Maria Jesus); Povés, C. (Carmen); Garau, C. (Catalina); Rodríguez-Alcalde, D. (Daniel); Herraiz, M. T. (María Teresa); Alvarez-Urturi, C. (Cristina); Dacal, A. (Andrés); Carrillo-Palau, M. (Marta); Cid, L. (Lucia); Ponce, M. (Marta)Background & Aims Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. Methods We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. Results The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%–65.2%) and 7.9% (95% CI, 5.2%–10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06–4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15–3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14–0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03–1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17–3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02–2.33). Conclusions Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.