Neolithic in ‘La Pileta’ Cave (Benaoján, Málaga)

Cueva de la Pileta es uno de los enclaves clásicos en la historiografía de la Prehistoria del sur de Iberia, sobre todo por las representaciones de arte rupestre. No obstante, el yacimiento también dispone de una amplia secuencia estratigráfica del Cuaternario reciente (p. ej., 7 m de potencia en la sala de los Murciélagos) que apenas ha recibido atención bibliográfica. Este trabajo se centra en la historiografía de los trabajos en el yacimiento y en el estudio de los materiales neolíticos. La colección cerámica y sus paralelos técnicos y estilísticos en el contexto del Mediterráneo y sur ibérico permiten integrar La Pileta dentro del primer Neolítico en Andalucía con una edad encuadrada en la segunda mitad del 8º milenio cal BP.Cave of La Pileta is a key site in southern Iberia prehistoric historiography. It’s mainly known for its rock art paintings, but the archaeological site also has a wide stratigraphic sequence of Recent Quaternary period (e.g. 7 meters in ‘Murciélagos’ Room) that has scarcely been studied. This paper focuses on historiographical analysis of worked areas and Neolithic materials. Ceramics and its stylistic and technical parallels in the Mediterranean and southern Iberian context allow us to classify Pileta in the first Neolithic period of Andalusia, second half of 8th millenium cal BP

Increased quality of life in patients with breakthrough cancer pain after individualized therapy : the CAVIDIOM study

Aim: To evaluate the quality of life (QoL) in patients with breakthrough cancer pain (BTcP) in Spanish medical oncology departments. Patients & methods: In a prospective, observational, multicenter study, we assessed QoL using the EQ-5D-5L instrument at baseline and after 15 and 30 days of individualized BTcP therapy, as well as BTcP characteristics and treatment. Results: Patients (n = 118) were mainly women, over 64 years old and with advanced cancer. QoL improved at 15 (p = 0.013) and 30 days (p = 0.011) versus baseline. Individualized BTcP therapy consisted mostly of rapid-onset opioids (transmucosal fentanyl at doses of 67-800 μg) according to the physician evaluation. BTcP improved, including statistically significant reductions in intensity, duration, number of episodes in the last 24 h and time to onset of BTcP relief. Conclusion: QoL increased after individualized pain therapy in patients with advanced cancer and BTcP in medical oncology departments. Keywords: breakthrough cancer pain; medical oncology; quality of life; rapid-onset opioids; transmucosal fentanyl

Risk and outcomes of COVID-19 in patients with multiple sclerosis

Background and purpose Limited information is available on incidence and outcomes of COVID-19 in patients with multiple sclerosis (MS). This study investigated the risks of SARS-CoV-2 infection and COVID-19-related outcomes in patients with MS, and compared these with the general population. Methods A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit admission, and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison. The study was conducted at 14 specialist MS treatment centers in Madrid, Spain, between February and May 2020. Results Two-hundred nineteen patients were included in the registry, 51 of whom were hospitalized with COVID-19. The mean age ± standard deviation was 45.3 ± 12.4 years, and the mean duration of MS was 11.9 ± 8.9 years. The infection incidence rate was lower in patients with MS than the general population (adjusted incidence rate ratio = 0.78, 95% confidence interval [CI] = 0.70–0.80), but hospitalization rates were higher (relative risk = 5.03, 95% CI = 3.76–6.62). Disease severity was generally low, with only one admission to an intensive care unit and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying treatment and hospitalization risk. Conclusions Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue disease-modifying treatment should be based on a careful risk–benefit assessment.post-print996 K

Prognostic value of the TGFβ1 rs4803455 single nucleotide polymorphism in small cell lung cancer

[Background] Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein β1 (HSPB1) and transforming growth factor β1 (TGFβ1) and survival have been investigated.[Methods] A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFβ1 gene and 5 of HSPB1 gene) variables were analyzed.[Results] The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFβ1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19–8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37–10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98–3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype.[Conclusions] Genetic analysis showed the CA genotype of TGFβ1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.Peer reviewe

MicroRNA Expression Profiling of Peripheral Blood Samples Predicts Resistance to First-line Sunitinib in Advanced Renal Cell Carcinoma Patients

Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC), but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood samples were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC. miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data. Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression. Blood samples from 38 patients and 287 miRNAs were evaluated. Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment. Predictive models identified populations with differences in the established end points. In the poor response group, median time to progression was 3.5 months and the overall survival was 8.5, whereas in the prolonged response group these values were 24 and 29.5 months, respectively. Ontology analyses pointed out to cancer-related pathways, such angiogenesis and apoptosis. miRNA expression signatures, measured in peripheral blood, may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib, improving diagnostic accuracy. After proper validation, these signatures could be used to tailor therapy in this setting

PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer

[Purpose] Germline mutations in DNA damage repair (DDR) genes are identified in a significant proportion of patients with metastatic prostate cancer, but the clinical implications of these genes remain unclear. This prospective multicenter cohort study evaluated the prevalence and effect of germline DDR (gDDR) mutations on metastatic castration-resistance prostate cancer (mCRPC) outcomes.[Patients and Methods] Unselected patients were enrolled at diagnosis of mCRPC and were screened for gDDR mutations in 107 genes. The primary aim was to assess the impact of ATM/BRCA1/BRCA2/PALB2 germline mutations on cause-specific survival (CSS) from diagnosis of mCRPC. Secondary aims included the association of gDDR subgroups with response outcomes for mCRPC treatments. Combined progression-free survival from the first systemic therapy (PFS) until progression on the second systemic therapy (PFS2) was also explored.[Results] We identified 68 carriers (16.2%) of 419 eligible patients, including 14 with BRCA2, eight with ATM, four with BRCA1, and none with PALB2 mutations. The study did not reach its primary end point, because the difference in CSS between ATM/BRCA1/BRCA2/PALB2 carriers and noncarriers was not statistically significant (23.3 v 33.2 months; P = .264). CSS was halved in germline BRCA2 (gBRCA2) carriers (17.4 v 33.2 months; P = .027), and gBRCA2 mutations were identified as an independent prognostic factor for CCS (hazard ratio [HR], 2.11; P = .033). Significant interactions between gBRCA2 status and treatment type (androgen signaling inhibitor v taxane therapy) were observed (CSS adjusted P = .014; PFS2 adjusted P = .005). CSS (24.0 v 17.0 months) and PFS2 (18.9 v 8.6 months) were greater in gBRCA2 carriers treated in first line with abiraterone or enzalutamide compared with taxanes. Clinical outcomes did not differ by treatment type in noncarriers.[Conclusion] gBRCA2 mutations have a deleterious impact on mCRPC outcomes that may be affected by the first line of treatment used. Determination of gBRCA2 status may be of assistance for the selection of the initial treatment in mCRPC. Nonetheless, confirmatory studies are required before these results can support a change in clinical practice.Supported by an unrestricted grant from Fundación Cris contra el cancer; three investigator awards from the Prostate Cancer Foundation (C.C.P. [2013], D.O. [2014], and E.C. [2017]); and three grants from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (No. PI13/01287 and PI16/01565 to D.O. and No. PI15/01471 to P.L.). During the conduct of this study, E.C., D.O., P.N., and L.M.-P. were supported by grants from Ministerio de Economía, Industria y Competitividad (No. JCI-2014-19129 [E.C.], No. RYC-2015-18625 [D.O.], No. SVP-2013-067937 [P.N.], No. SVP-2014-068895 [L.M.]); D.O. was also funded by a Return fellowship from Fundación Científica de la Asociación Española Contra el Cancer, 2012-2015; N.R.L. and R.L., by grants from Instituto de Salud Carlos III (No. CM14-00200 to N.R.L. and No. CM17-00221 [R.L.]); and Y.C., by a grant from Ministerio de Educación, Cultura y Deportes (No. FPU15/05126). C.C.P. was supported by a congressional-designated medical research program award (No. CMRP-PC131820).Peer reviewe