Initial clinical and treatment patterns of advanced differentiated thyroid cancer: ERUDIT study.

Background: Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective: The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods: A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results: Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3-15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7-16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0-2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05). Conclusion: Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.

Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial.

Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases.

Guía de práctica clínica de carcinoma de células de merkel: diagnóstico y tratamiento en atención especializada dermatológica / Merkel cell carcinoma clinical practice guide: diagnosis and treatment in specialized dermatological care

El carcinoma de células de Merkel (CM) es un tumor cutáneo infrecuente (0.28 (95% CI: 0.15-0.40) casos por 100 000 personas año) y agresivo. El diagnóstico inicial y el estadiaje presentan variabilidad, y las técnicas a emplear podrían no estar disponibles en todos los centros. Por otro lado, la baja incidencia dificulta en muchos centros el poder adquirir experiencia. Existen guías de práctica clínica para el cuidado del CM, pero en contextos diferentes y con una cobertura parcial de los problemas que los dermatólogos han identificado como principales. Por ello, la Fundación Piel Sana AEDV, ha impulsado la adaptación de Guías de Práctica Clínica (GPC) sobre el CM, formando parte del proyecto Libro Blanco del Cáncer Cutáneo. El objetivo de esta guía es mejorar la calidad asistencial de los pacientes con CM, utilizando recomendaciones adaptadas a nuestro medio y basadas en los datos más válidos posibles. Esta guía revisa las principales técnicas diagnósticas empleadas en el diagnóstico inicial y estadiaje, así como los procedimientos terapéuticos para los tumores localizados.

Biweekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer.

OBJECTIVE: The combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC. PATIENTS AND METHODS: Patients aged ≥70years with previously untreated MCRC received oxaliplatin 85mg/m(2) on day 1, every 2weeks plus capecitabine 1000mg/m(2) (or capecitabine 750mg/m(2) if creatinine clearance was 30-50mL/min) twice daily on days 1-7, every 2weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12cycles. RESULTS: Thirty-five patients were enrolled. Median age was 78years (range, 70-83). Patients received a median of 11cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5-11.7) and 15.5 (95% CI: 9.6-21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1-2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death. CONCLUSION: Our findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC.