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Introduction Systemic treatment options for patients with hormone-refractory prostate cancer (HRPC) that progress despite the use of Docetaxel are very limited. One of the options of compassionate use currently available is the use of Sunitinib. We present a joint preliminary experience with the use of Sunitinib in this clinical case. Patients and methods A series of eight cases is presented, which sets forth a prospective multicentre experience with Sunitinib in patients with hormone-refractory metastatic and progressive prostate cancer, previously treated with at least a regimen of Docetaxelbased chemotherapy. Other alternative chemotherapy regimes had already been tried in some patients. The primary objective of our study was the PSA response rate and our secondary objective was the progression-free period. We administered a dosage of 50 mg/day for four-week cycles, followed by a two-week rest per cycle, until we reached a total of eight cycles or up to clinical progression or intolerable toxicity. Results In four cases, the PSA dropped to below 50% of the baseline level at the beginning of the treatment, and five patients presented some decrease in PSA. The progression-free time was 16.4 weeks. Toxicity arising from the treatment was moderate and manageable. Conclusions Despite the limits of this experience, we can say that Sunitinib appears to be an active and safe option in patients with hormone-refractory prostate cancer that is resistant to chemotherapy with Docetaxel.

The magnetic structure of amorphous and thermal annealed glass coated microwires is studied by thermomagnetic, DSC, and Bitter domain pattern techniques. The long-range dipolar interaction between parallel aligned microwires and the appearance of large Barkhausen jumps steps in the axially magnetized loops are discussed in terms of reversal magnetization process.

Magnetostrictive microwires exhibit bistable magnetic behavior characterized by square hysteresis loops, a consequence of the magnetization reversal by depinning of a single domain wall from the closure structure at one end of the wire. This bistable behavior spontaneously observed in magnetostrictive microwires has been previously thoroughly studied at room temperature. In the present work, the temperature dependence of the remagnetization process is investigated in magnetic microwires, a few micrometres in diameter, covered by glassy coating plus additional metallic coatings. The influence first of geometrical parameters as length and diameter is considered. Later on, an emphasis is placed on the influence of the Pyrex and additional sputtered and electroplated coatings on the temperature dependence of switching field. Bistability can be lost, depending on the character of the coating, when reducing the measuring temperature due to the thermally induced anisotropy arising from the differential thermal expansion coefficient of the composite wire. On the other hand, the temperature dependence of the switching field and its distribution function have been measured. It is shown that the switching field increases as temperature decreases, which is analyzed considering the thermally activated pinning mechanism and the magnetostrictive contribution.

The objective of the treatment in stages III A and III B without pleural effusion should be both locoregional and distant disease control. We known that at least 80% of the patients had micrometastatic disease at the time of diagnosis, so that a treatment that is only local would be condemned to failure from the time it is suggested. Many clinical questions continue to exist and each step achieved is followed by a new diagnostic or therapeutic dilemma and is thus a fertile field for clinical research.

Cisplatin plus oral vinorelbine, one of the standard treatments for metastatic non-small-cell lung cancer (NSCLC), is associated with a high rate of neutropenia, and a hemogram is performed on day 8. We analyzed the oncologists' opinions and the result of the hemogram on day 8 to address the question of whether this hemogram could be avoided.Fifty-eight chemotherapy-naive, advanced NSCLC patients were included. Each received intravenous doses of 75 mg/m(2) cisplatin on day 1 plus oral vinorelbine [60 mg/m(2) in the first cycle (80 mg/m(2) in subsequent cycles) on days 1 and 8], every 3 weeks, for a maximum of six cycles.Out of 257 cycles analyzed, oral vinorelbine was administered on day 8 in 214 (83.2 %) and the dose was canceled in 6 cycles (2.3 %) due to hematological toxicity. On analyzing the patients to whom chemotherapy had been administered on day 8, based on medical opinion without the doctor knowing the hemogram result, we found that the cycle had been administered with a hemogram showing fewer than 1,500 × 10(6) neutrophils in only 3 of the 185 evaluable cycles [event rate of 1.6 %, with confidence interval 95 % = (0.34-4.67 %)].The hemogram on day 8 can be avoided and oral vinorelbine administered in relative safety in patients with good performance status, when confirmed by the clinician's perception, thereby making this regimen more comfortable for the patient. This is the first prospective study to examine this issue.

Resumen Introduccion las opciones de tratamiento sistemico para los pacientes con cancer de prostata hormonorrefractario (CPHR) que progresan a pesar del uso de docetaxel son muy limitadas. Una de las opciones de uso compasivo disponibles en la actualidad es el empleo de sunitinib. Presentamos una experiencia preliminar conjunta con el uso de sunitinib en esta circunstancia clinica. Pacientes y metodos se presenta una serie de 8 casos que refleja una experiencia multicentrica prospectiva con sunitinib en pacientes con cancer de prostata metastatico, hormonorrefractario y en progresion, previamente tratados con al menos un regimen quimioterapico a base de docetaxel. En algunos pacientes ya se habian ensayado otros regimenes quimioterapicos alternativos. El objetivo primario de nuestro estudio fue la tasa de respuesta de PSA, y el objetivo secundario el tiempo libre de progresion. Se administro una dosis de 50 mg/ dia durante ciclos de 4 semanas, seguidos de 2 semanas de descanso por ciclo, hasta alcanzar un total de 8 ciclos o hasta la progresion clinica o toxicidad intolerable. Resultados en 4 casos el PSA descendio por debajo del 50% del nivel basal al inicio del tratamiento, y 5 pacientes presentaron algun descenso del PSA. El tiempo libre de progresion fue de 16,4 semanas. La toxicidad derivada del tratamiento fue moderada y manejable. Conclusiones a pesar de lo limitado de esta experiencia, podemos decir que sunitinib parece una opcion activa y segura en pacientes con cancer de prostata hormonorrefractario y resistente a quimioterapia con docetaxel.

The results of the recently performed randomised trials support the conclusion that adjuvant chemotherapy confers survival advantage in early stage in non-small cell lung cancer, and now has become the standard of care for patients with resected stage II and IIIA. The role of adjuvant chemotherapy for stage I disease remains controversial. Only some patients benefit from systemic adjuvant therapy and we need to identify factors of patients most likely to respond to chemotherapy. The purpose of this article is to provide a general overview of adjuvant chemotherapy for early stage in non-small cell lung cancer.

La tomografía por emisión de positrones con 2-(18F)-fluoro-2-desoxi-D-glucosa (PET-FDG) es una técnica metabólica de imagen. La PET-FDG es más precisa que el CT en la valoración de la afectación mediastínica en los pacientes con carcinoma de pulmón no microcítico, con un alto valor predictivo negativo. Puede detectar metástasis ocultas en el 11% de los pacientes, si bien, la etiología de las captaciones solitarias extratorácicas debe ser confirmada. La PET-FDG, teóricamente, puede influir en el volumen de planificación de la radioterapia, sobre todo en los pacientes con atelectasia. La cuantificación de la actividad metabólica mediante la PET-FDG está influenciada por el tamaño de la lesión, los niveles de glucosa, el tiempo que transcurre desde la inyección del isótopo. Se necesitan más ensayos clínicos para la estandarización de los métodos de realización del PET, su uso como factor pronóstico y para la valoración de la respuesta al tratamiento.

The objective of the treatment in stages III A and III B without pleural effusion should be both locoregional and distant disease control. We known that at least 80% of the patients had micrometastatic disease at the time of diagnosis, so that a treatment that is only local would be condemned to failure from the time it is suggested. Many clinical questions continue to exist and each step achieved is followed by a new diagnostic or therapeutic dilemma and is thus a fertile field for clinical research.

Parte del número especial: Proceedings of the Joint European Magnetic Symposia (JEMS' 04) A novel technique involving combined sputtering and electroplating procedures has been recently developed to deposit metallic (magnetic or not) nano and microlayer tubes onto glass-coated amorphous magnetic microwires to enable the tailoring of their magnetic behavior. Here, after introducing the general aspects of that technique, we present the latest results on a new family of two-phase magnetic samples: bi-magnetic multilayer microwires. They consist of a magnetically soft nucleus (typically a Fe or Co base amorphous microwire, coated by Pyrex layer) onto which a 30 nm thick Au layer is first sputtered followed by the electroplating of a harder microlayer, namely CoxNi(1−x) layer, with x controlled by the current density during electrodeposition whose micrometric thickness is also controlled by plating time. The hysteresis loops present a two-step reversal process typical of two-phase magnetic material. The magnetization reversal of the soft nucleus and the harder layer takes place at around 1 Oe and up to about 200 Oe, respectively. The presence of sputtered and electroplated layers induces significant stresses in the soft magnetic nucleus that modify its magnetization easy axis. This technique allowing us the tailoring of the magnetic behavior of multilayer magnetic microwires opens new possibilities for applying these novel materials as sensing elements in various devices.

Aim: Patients cured of Hodgkin Lymphoma (HL) have an increased risk of developing Second Neoplasms (SN). We compared characteristics of patients with Thoracic malignancies (TM), (lung cancer or mesothelioma) to other SN. Methods: 604 patients treated of HL and monitored in our hospital from 1968 to 2012 were retrospectively analyzed. Results: We found 90 (14.5%) SN: 27 (30%) patients developed TM and 63 (70%) other SN. Median age at HL diagnosis was similar in both groups (p=0.31) whereas elapsed time until SN diagnosis was 16.5 and 11.0 years respectively (p=0.004). In TM group, 85.5% of patients were men (p=0.001) and 85.2% were smokers (RR 3.4 CI95% 1.3-8.9, p=0.003). Concerning HL stage at diagnosis 25.9% in TM and 50.8% in other SN had advanced stages (p=0,029). Chemotherapy treatments received for HL were similar in both groups whereas radiotherapy when compared with combined treatment or chemotherapy was associated with an increased risk of TM (RR=2.3, CI 95% 0.9-5.9 p=0.07).The majority (59.2%) of patients with TM were diagnosed after consulting for new symptoms and had advanced stages. Adenocarcinoma was the most prevalent histology. Overall survival at 1 and 5 years in TM and other SN group was 59%/62%, and 24%/41% respectively (p=0.05). Considering the 604 patients, cumulative incidence of SN in general at ten and twenty-five years was 7.6% and 31.3% respectively and in TM group 1.5% and 9.7%. Conclusions: Smoking habit, male gender as well as radiotherapy are associated to the development of TM. Patients diagnosed of advanced stages of HL develop more frequently other SN. Moreover we found longer elapsed time until diagnosis of SN in TM group and shorter overall survival. The role of SN screening has yet to be prospectively evaluated. Disclosure: All authors have declared no conflicts of interest.

Aim: Hepatitis infection has a high prevalence in patients with non-Hodgkin lymphoma. Our objective is to evaluate clinical characteristics and survival of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) who are hepatitis B and/or C (HBV/HCV) positive. Methods: We reviewed 224 patents diagnosed with DLBCL in our hospital between October 1982 and September 2013. Clinical, treatment and following items were obtained. Results: We found 21 positive HBV and/or HCV (9.3%) [4 of them (1.78%) were both positive], and 203 (90.7%) negative virus (NV), without significant differences in baseline characteristics. 14 patients (67%) with HBV-C were diagnosed in stages III and IV, while 78 (40.1%) of NV were diagnosed in advanced stages. Significant differences were found in number of nodal regions affected, 4 in HBV/HCV positive vs 2 in NV, and in liver involvement which was greater in HBV/HCV positive (28.6% vs 10%, p = 0.028). 55.9% patients (n = 105) with NV were treated without rituximab, and 44.1 (n = 83) with rituximab, while 36.8% patients (n = 7) with positive virus were treated without rituximab, and 63.2% (n = 12) with rituximab. The others patients were treated with surgery, radiotherapy or did not receive any treatment due to poor performance status and comorbidities. Neither was any differences found with respect to response or number of relapses. We did not find significative toxicity after chemotheraphy, and there were no differences according the presence or absence of hepatitis virus. Liver toxicity was mainly grade 0-2. Liver toxicity grade 3 or more was found only in 1 patient. In the long term follow up of patients alive we did not find significative long-term liver complications grade 3 or more in any patient of the two groups. There were no differences in the study of the causes of death either. No significant differences in the relative risk of death associated with virus (HR 0.87 (CI 95% 0.40-1.89, p = 0.73) and the relative risk of events associated with virus (HR 0.96 (CI 95% 0.48-1.90, p = 0.91) were found. No significant differences were found with respect to the probability of overall or disease free survival. Conclusions: Despite the differences found with respect to the stage, total number of nodal regions affected and liver involvement, HBV/HCV positive and VN DLBCL patients should receive the same treatment and they respond and evolve equally. Disclosure: All authors have declared no conflicts of interest.

Aim: The Spanish Lung Cancer Group (SLCG) undertook an industry-independent, two biomarker-directed, randomized trial in advanced NSCLC p. The study (NCT00617656/GECP-BREC) compared non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 mRNA levels. The trial was closed prematurely due to a detrimental effect in the biomarker-directed arm. Further genetic analysis defined PALB2, the bridging molecule that connects BRCA1 and BRCA2, as a promising biomarker to elucidate DNA repair mechanisms. Methods: We assessed mRNA levels of PALB2, RIF1, 53BP1, RNF8 and ATM (as biomarkers with critical roles in homologous recombination [HR]) in tissue from 177 cisplatin plus docetaxel-treated NSCLC p in the BREC trial. We correlated our findings with PFS, OS and response. Results: Median age 62; 79.1% male; 51.4% adenocarcinoma. Results of PALB2 mRNA expression were intriguing. PFS was 5.6 months (m) for p with high/intermediate (H-I) PALB2 and 4.1 m for p with low (L) PALB2 (p = 0.0018). OS was 13.2 m for p with H-I PALB2 compared to 9.9 for p with L PALB2 (p = 0.0377). In the univariate analysis, H-I PALB2 was a marker of longer PFS (HR = 0.56, 95% CI, 0.38, 0.80; p = 0.002) and OS (HR = 0.64, 95% CI, 0.41, 0.98; p = 0.0394). In the multivariate analysis, only H-I PALB2 was associated with longer PFS (here HR = 0.56 and p = 0.0022) and OS (HR = 0.61 and p = 0.0343). Among 143 p with data for response and PALB2 expression, 49.5% of p with H-I PALB2 were responders, compared to only 28% with L PALB2 (p = 0.0131). No significant differences were found for PFS, OS or response according to expression status of the other 4 biomarkers. Conclusions: Our findings reveal PALB2 to be a predictive and prognostic biomarker in advanced NSCLC p treated with docetaxel plus cisplatin. The BRCA1-PALB2-BRCA2 network is a critical determinant of responsiveness to DNA interstrand cross-linking agents and antimicrotubule agents. In our study, BRCA1 had no effect on treatment outcome of this population. PALB2 was found to be a strong marker to predict sensitivity to antimicrotubule agents, without affecting sensitivity to DNA damage-based chemotherapy. Disclosure: All authors have declared no conflicts of interest.

Aim: Preclinical data show that A, an irreversible ErbB family blocker, combined with an mTOR inhibitor such as S, may restore sensitivity in EGFR M+ NSCLC pts who progress after E/G. This trial was conducted to identify the maximum tolerated dose (MTD) of A + S. Methods: Pts with stage IIIB/IV NSCLC who failed ≥1 prior treatment, and whose tumour was EGFR M + , or negative/unknown, but had progressive disease after response or stable disease (SD) for ≥6 months on prior E/G were eligible. Pts received run-in treatment with sirolimus for 8 days before starting the combination therapy. Definition of MTD was initially based on dose-limiting toxicities (DLTs) in cycle (C) 1 (28 days) but with an amendment this was extended to C1 and 2. EGFR mutation was assessed (from blood and archival tumour) and PK sampling was performed. Tumour assessment was performed at week 4, 8, 12, then every 8 weeks. Results: 39 pts were treated: median age 61y (range: 32-81); male: 15; ECOG 0/1/2: 16/21/1; adeno/squamous/large cell carcinoma: 33/3/3. All had prior E/G; 32 had ≥1 prior chemotherapy. Median treatment duration: 103 days (range: 10-367). Pts were treated at 6 dose levels (A, mg/S, mg): 30/1 (n = 12), 40/1 (n = 3), 30/3 (n = 9), 30/5 (n = 9), 30/10 (n = 3), 40/5 (n = 3), with 30/1 defined as MTD. DLTs (C1 and 2) were seen in 12 pts (Table). The most frequent (≥20%, all grades) drug-related adverse events were: diarrhoea, mucositis, rash, asthenia, decreased appetite and nausea. The best response was partial response (PR) in 4 pts (2 at 30/5, 2 at 40/5); 23 had stable disease (SD) (median duration [days]: 105, range: 51-337). PK, tumour and blood mutation results will be presented. DLTs (grade [n]) by dose level 30/1 40/1 30/3 30/5 30/10 40/5 Diarrhoea – G3 (1) G3 (1) – G3 (2)* G3 (1) Mucositis – – G3 (1) G3 (2) G3 (1) G3 (2) Raised CPK – G4 (1) – – – – *1 pt had G3 diarrhoea, asthenia, anorexia and iliac fossa pain. Conclusions: A + S combination had limited tolerability in pts with EGFR M+ NSCLC progressing on E/G mainly due to overlapping DLTs of diarrhoea and mucositis. A 30 mg + S 1 mg was defined as MTD. PRs were observed at doses exceeding MTD; SD was observed at all doses. Disclosure: M. Majem: Membership on an advisory board for Roche, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer; N. Reguart: Membership on an advisory board for Roche, Lilly, Boehringer Ingelheim and Pfizer; C.P. Lee: Employee of Boehringer Ingelheim; S. Kraemer: Employee of Boehringer Ingelheim; D. Schnell: Employee of Boehringer Ingelheim. All other authors have declared no conflicts of interest.

In 95 breast carcinomas, we investigated P14ARF and TP73 mRNA expression and their relationship to TP53 mutations, determined by an immunohistochemical method, studying several clinicopathologic features of the tumors. P14ARF and TP73 mRNA levels were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR), using beta-actin as a control. P14ARF was overexpressed in 19% of the cases and underexpressed in 24%. TP73 was overexpressed in 22% of the tumors, and normal levels were found in the remaining 78%. The analysis of TP53 showed positive immunostaining in 38% of cases. The association of P14ARF and TP73 overexpression was statistically significant, as was the association between positive TP53 staining and TP73 overexpression. P14ARF was related to TP53 only in those cases in which there was low expression of P14ARF. Concomitant overexpression of P14ARF and TP73 was statistically related to positive TP53 immunostaining. The analysis of concomitant P14ARF and TP73 overexpression and clinicopathologic parameters of the tumors showed a statistically significant difference with respect to peritumoral vessel invasion (P = 0.01), lymph node metastasis (P = 0.03), negative ERBB2 expression (P = 0.005), and more advanced pathologic stages (P = 0.03). These results suggest that overexpression of P14ARF and TP73 could be implicated in breast carcinoma tumorigenesis and, ultimately, in the phenotypic features of these lesions.