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The number of effective systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC) is rapidly increasing, and the advent of immunotherapy has changed the treatment paradigm for these patients, leading to significantly improved survival outcomes. However, many patients with HCC will continue to receive tyrosine kinase inhibitors, partly because of contraindications to immune checkpoint inhibitors. Currently, the best sequential first- and second-line systemic treatment remains elusive. Maintenance of optimal liver function is crucial, it is likely to impinge on temporary or permanent treatment discontinuation, and should also be considered when defining the treatment sequence. Hepatic decompensation, which does not always coincide with disease progression, is part of this complex dynamically evolving system, and must be promptly recognized and adequately managed to allow the patient to continue in the therapeutic course. The purpose of this review is to highlight and summarize the evidence on the efficacy and safety of systemic agents, with a focus on the impact of underlying cirrhosis, and to suggest new clinical outcomes for randomized controlled trials for advanced HCC to better assess the net health benefit in this specific setting.

Objective: The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario. Background data: The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. Methods: BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups. Results: Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. Eastern Cooperative Oncological Group Performance Status (ECOG-PS), presence of cirrhosis, steatosis, Child-Pugh grade, hepatitis B virus and hepatitis C virus, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG = 374 and SOR = 263. After IPW, 1-3-5 years OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (P < 0.001). Similar trends were observed after subgrouping patients by ECOG-PS = 0 and ECOG-PS >0, and by the intrahepatic location of portal vein invasion. At Cox regression, sorafenib treatment (hazard ratio 4.436; 95% confidence interval 3.19-6.15; P < 0.001) and Charlson Index (hazard ratio 1.162; 95% confidence interval 1.06-1.27; P = 0.010) were the only independent predictors of mortality. PFS at 1-3-5 years were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (P = 0.007). Conclusions: In BCLC C patients without extrahepatic spread but with intrahepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.

Acne is a chronic inflammatory condition affecting the pilosebaceous unit that was traditionally viewed as a disease of the adolescence. However, over the past several years, an increasing number of adult women have been reported to suffer from this condition. The prevalence of adult female acne ranges between 12 and 54%. Two clinical types can be distinguished in this population, a 'retentional' and an 'inflammatory' type, which usually tend to overlap. In terms of evolution, three main subtypes can be identified: Persistent acne, which is the most frequent subtype, late-onset acne and recurrent acne. This type of acne is mainly mild-to-moderate in severity and may be refractory to conventional treatment. The etiopathogenesis is complex and has yet to be fully elucidated. It appears to involve an interaction among genetic predisposition, hormonal factors, and chronic activation of the innate immune system overlapping with external factors, such as daily stress, Western-type diet, use of tobacco and cosmetics. The treatment may be challenging and a holistic approach is required, with special attention to the individual needs and particularities of adult women. Both topical and systemic treatments are available, with hormonal therapies being of special value in this population. The aim of the present article was to provide up-to-date, evidence-based information on the clinical presentation, etiopathogenesis and treatment of adult female acne.

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia A Psoríase é uma doença inflamatória de carácter crónico do foro dermatológico e que afeta essencialmente a epiderme, podendo, ao longo do tempo, evoluir a nível sistémico, bem como ser associado a diversas comorbilidades. Tanto o início da psoríase como as exacerbações da doença podem estar relacionadas com fatores ambientais, genéticos e imunológicos.Existem diversos subtipos clínicos da psoríase, sendo os mais comuns e os que serão objeto desta revisão a psoríase em placas, psoríase inversa, psoríase gutata, psoríase pustulosa, psoríase eritrodérmica, psoríase palmo-plantar, psoríase ungueal e artrite psoriática, esta última podendo também ser considerada uma comorbilidade estando associada a uma evolução a longo prazo da psoríase.Por ser uma doença sem cura, o objetivo terapêutico é a gestão da doença e evitar a exposição aos fatores “gatilho”, que podem ser diferentes para cada caso. Assim, torna-se essencial estabelecer uma terapêutica personalizada a cada doente e um acompanhamento ativo da evolução da doença e do próprio portador de psoríase.Nesta revisão serão abordados os aspetos patológicos da psoríase, os seus subtipos, etiologia e sintomatologia associada aos mesmos, a sua fisiopatologia, assim como o seu impacto a nível socioeconómico e da qualidade de vida. Serão também apresentadas as diversas terapêuticas existentes no mercado e as emergentes, possíveis efeitos secundários e, por fim, será discutido o futuro do tratamento da psoríase, bem como o panorama em Portugal no que concerne às terapias disponíveis e à informação e apoio ao doente com psoríase. Psoriasis is a chronic inflammatory disease of dermatological nature that essentially affects the epidermis, which may, over time, evolve at a systemic level, as well as being associated with several comorbidities. Both the onset of psoriasis and the exacerbations of the disease may be related to environmental, genetic and immunological factors.There are several clinical subtypes of psoriasis, the most common and the ones to be discussed in this review are plaque psoriasis, inverse psoriasis, guttate psoriasis, pustular psoriasis, erythrodermic psoriasis, palmoplantar psoriasis, nail psoriasis and psoriatic arthritis, the last one being considered a comorbidity due to its association with a long-term evolution of psoriasis.As it is an incurable disease, the therapeutic goal is to manage the disease and avoid exposure to “trigger” factors, which may be different for each case. Thus, it is essential to establish a personalized therapy for each patient and actively monitoring the evolution of the disease and the psoriasis patient.This review will address the pathological aspects of psoriasis, its subtypes, etiology, associated symptomatology, its pathophysiology, as well as its impact on the socioeconomic level and on the patient’s quality of life. The various therapies currently on the market and emerging therapies will also be presented, as well as possible side effects and, finally it will be discussed the current scenario in Portugal regarding the available therapies and the information and support for patients with psoriasis; and what is expected for the future of psoriatic therapy.

Purpose of review To review the latest in penile cancer treatment focusing on neoadjuvant chemotherapy in patients with regional lymph node involvement. Recent findings Patients with regional lymph node involvement from penile cancer still suffer from a poor prognosis, and the chances to achieve cure are primarily dependent on the extent of the disease. Despite multiple lines of research are indicating the need for a multimodal management of the disease upfront, the search for newer effective systemic therapies is ongoing. The available guidelines currently suggest the use of combination chemotherapy regimens including taxanes and cisplatin as induction therapy before lymphadenectomy in patients with locally advanced disease (i.e., fixed or bulky inguinal lymph nodes or pelvic lymph node involvement). Research in the field will aim to provide more effective systemic therapies also in patients with a more limited disease spread to further improve the outcomes. Data from the literature also indicate the possibility to effectively administer postoperative chemotherapy in selected high-risk patients. Summary We aimed to provide the evidence from the literature and the new avenues that would help delineating the optimal therapeutic pathway for these complex patients, commenting on the new opportunities that may come from the ongoing research.

[Background] Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm arising from the synovium of joints, bursae, and tendon sheaths affecting small and large joints. It represents a wide spectrum ranging from minimally symptomatic to massively debilitating. Most findings to date are mainly from small, retrospective case series, and thus the morbidity and actual impact of this rare disease remain to be elucidated. This study prospectively explores the management of TGCT in tertiary sarcoma centers., [Methods] The TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study involving 12 tertiary sarcoma centers in 7 European countries, and 2 US sites. This study enrolled for 2 years all consecutive ≥ 18 years old patients, with histologically diagnosed primary or recurrent cases of diffuse-type TGCT. Patient demographic and clinical characteristics were collected at baseline and every 6 months for 24 months. Quality of life questionnaires (PROMIS-PF and EQ-5D) were also administered at the same time-points. Here we report baseline patient characteristics., [Results] 166 patients were enrolled between November 2016 and March 2019. Baseline characteristics were: mean age 44 years (mean age at disease onset: 39 years), 139/166 (83.7%) had prior treatment, 71/166 patients (42.8%) had ≥ 1 recurrence after treatment of their primary tumor, 76/136 (55.9%) visited a medical specialist ≥ 5 times, 66/116 (56.9%) missed work in the 24 months prior to baseline, and 17/166 (11.6%) changed employment status or retired prematurely due to disease burden. Prior treatment consisted of surgery (i.e., arthroscopic, open synovectomy) (128/166; 77.1%) and systemic treatments (52/166; 31.3%) with imatinib (19/52; 36.5%) or pexidartinib (27/52; 51.9%). Treatment strategies at baseline visits consisted mainly of watchful waiting (81/166; 48.8%), surgery (41/166; 24.7%), or targeted systemic therapy (37/166; 22.3%). Patients indicated for treatment reported more impairment compared to patients indicated for watchful waiting: worst stiffness NRS 5.16/3.44, worst pain NRS 6.13/5.03, PROMIS-PF 39.48/43.85, and EQ-5D VAS 66.54/71.85., [Conclusion] This study confirms that diffuse-type TGCT can highly impact quality of life. A prospective observational registry in rare disease is feasible and can be a tool to collect curated-population reflective data in orphan diseases., [Name of registry] Tenosynovial Giant Cell Tumors (TGCT) Observational Platform Project (TOPP)., [Trial registration number] NCT02948088., [Date of registration] 10 October 2016., [URL of Trial registry record] https://clinicaltrials.gov/ct2/show/NCT02948088?term=NCT02948088&draw=2., Sponsored by Daiichi Sankyo, Co., Ltd; ClinicalTrials.gov Number NCT02948088. The Department of Orthopaedics of the Leiden University Medical Center receives research funding from Daiichi Sankyo. All research funding for Memorial Sloan Kettering is supported in part by a grant from the National Institutes of Health/National Cancer Institute (#P30 CA008748).

Simple Summary Hepatocellular carcinoma is a frequent and poor prognosis tumor, with most patients facing up, soon or later, to systemic therapies. So far, systemic therapies based on tyrosine kinase inhibitor monotherapies have been of modest benefit. The aim of this review article was to characterize the profile of efficacy and safety of immuno-oncology-based monotherapies that failed to demonstrate significant benefit, for comparison with the immuno-oncology-based combinational strategies. One of them has proven its drastic benefit in phase-3, whereas others have only shown promising data in phase-1/2, although the corresponding phase-3 results are pending. We showed that objective response rates and duration of response are important parameters for increased median overall survival and long survivals. We also pointed out that, being aware that there is an urgent unmet need for biomarkers, the pattern of safety and quality of life will guide the physician for the choice on the possible future combinations. Abstract Hepatocellular carcinoma is a poor prognosis tumor. Systemic therapies are frequently used due to frequent recurrences after surgical or radiologic treatments. Anti-angiogenic tyrosine kinase inhibitors have shown efficacy in monotherapy, but with very low rates of long survival and exceptional recovery. Immuno-oncology based on immune checkpoint inhibitors has revolutionized the systemic therapies since showing long survival rates without any tumor progression or recurrence for some patients in partial or complete response, and possibly for some patients in stable disease. However, the rate of responders under immuno-oncology monotherapy is too low to increase significantly the median overall survival of the treated patients. The immuno-oncology-based combinations with different types of immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 inhibitors such as nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, tremelimumab), or the association of immune checkpoint inhibitors plus anti-angiogenic agents (bevacizumab, lenvatinib, cabozantinib), have led to a breakthrough in the treatment of hepatocellular carcinoma. Indeed, the first phase-3 trial, combining atezolizumab with bevacizumab, has dramatically changed the outcome of patients. Data from several other types of combinations assessed in phase-3 trials are pending, and if positive, will drastically arm the physicians to efficiently treat the patients, and disrupt the current algorithm of hepatocellular carcinoma treatment.

Treatment of advanced hepatocellular carcinoma (HCC) is challenging. Several randomized clinical trials are investigating the efficacy of systemic therapy, immunotherapy, and locoregional therapy as monotherapy or combined with other modalities in the treatment of HCC. Systemic therapy is the preferred treatment in advanced disease. To date, multiple first-line and second-line agents received Food and Drug Administration approval. For over a decade, sorafenib was the only first-line agent. In May 2020, combination of atezolizumab and bevacizumab has been approved as a first-line systemic regimen. Lenvatinib is another first-line agent that has multikinase activity. Second-line agents include cabozantinib, regorafenib, ramucirumab, and nivolumab. Adoptive cell transfer therapy is a highly specific immunotherapy that has shown antitumor activity against HCC. Oncolytic viruses are genetically modified viruses that infect cancer cells and induce apoptosis. Locoregional therapies such as transarterial chemoembolization and radioembolization have shown a potential benefit in selected patients with advanced HCC. In this review, we aim to summarize the treatment options available for advanced HCC.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common—paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Cancer during pregnancy is a challenge for multi- and interdisciplinary collaboration due to the diagnostic, prognostic and therapeutic implications, the need for an integrated harmonization of medical action for the pregnant patient and the embryo or foetus and the characteristics of each gestational period, which will determine the protocol to be proposed and its limitations. For this reason, a group of experts appointed by participating scientific societies, which includes the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM), the Spanish Association of Surgeons (Asociación Española de Cirujanos—AEC), the Spanish Society of Gynaecology and Obstetrics (Sociedad Española de Ginecología y Obstetricia—SEGO), the Spanish Society of Nuclear Medicine and Molecular Imaging (Sociedad Española de Medicina Nuclear e Imagen Molecular—SEMNIM), the Spanish Society of Oncological Radiotherapy (Sociedad Española de Oncología Radioterápica—SEOR) and the Spanish Society of Medical Radiology (Sociedad Española de Radiología Médica—SERAM), have worked together to establish consensus recommendations that allow the harmonization of management and ultimately the optimization of the healthcare of pregnant patients with cancer. When cancer is detected in a pregnant woman, the week of gestation in which the diagnosis is made must be considered, as well as the characteristics of the tumour. It is strongly recommended that a multidisciplinary team assesses the situation and guides the patient and her family during the informing, diagnosis and treatment process. Likewise, the foetus should be monitored and managed by specialized obstetricians who are part of a multidisciplinary cancer committee.

Contains fulltext : 220839.pdf (Publisher’s version ) (Closed access) BACKGROUND: Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. METHODS: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. RESULTS: Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. CONCLUSION: This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.

Aim To evaluate clinical outcome in locally-advanced stage IV (M0) head and neck cancer patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) in daily clinical practice. Background Despite SIB-IMRT has been reported as a feasible and effective advanced head and neck cancer treatment, there are few data about its concurrent use with systemic therapies. Material and Methods We reviewed 41 staged IV (M0) head and neck cancer patients treated in two radiotherapy units in the city of Messina (Italy) during the last six years, using intensity modulated techniques-SIB. 22/41 patients had concomitant chemotherapy or cetuximab. Acute and late toxicities, objective response (OR) rate, local control (LC) and overall survival (OS) have been evaluated. Results 37/41 patients received the planned doses of radiotherapy, 2 patients died during the therapy. The major acute regional toxicities were skin reaction and mucositis. A case of mandibular osteoradionecrosis was recorded. At completion of treatment, OR was evaluated in 38 patients: 32/38 patients (84.2%) had complete (55.3%) and partial (28.9%) response. The 1- and 5-year LC rates were 73.4% and 69.73%, respectively. The 1-, 3-, and 5-year OS rates were 85.93%, 51.49% and 44.14%, respectively. No statistically significant differences in outcomes have been observed in patients treated with radiotherapy alone vs. irradiation concomitant to chemo/biotherapy. The median OS was 45 months. Conclusion SIB-IMRT is safeand can be used with concomitant chemotherapy/biotherapy in real-life daily clinical practice. SIB-IMRT alone is a valid alternative in patients unfit for systemic therapies.

Background Aberrant activation of Axl is implicated in the progression of hepatocellular carcinoma (HCC). We explored the biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naive and resistant HCC. Methods We evaluated Axl expression in sorafenib-naive and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays. Results Axl mRNA overexpression in cell lines (n = 28) and RNA-seq tissue datasets (n = 373) correlated with epithelial-to-mesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and normal liver. We confirmed sorafenib resistance to be associated with EMT and enhanced motility in both HuH7-SR and SKHep-1-SR cells documenting a 4-fold increase in Axl phosphorylation as an adaptive feature of chronic sorafenib treatment in SKHep-1-SR cells. Axl inhibition reduced motility and enhanced sensitivity to sorafenib in SKHep-1SR cells. In patients treated with sorafenib (n = 40), circulating Axl levels correlated with shorter survival. Conclusions Suppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance.

In 2010, modified RECIST (mRECIST) criteria were proposed as a way of adapting the RECIST criteria to the particularities of hepatocellular carcinoma (HCC). We intended to overcome some limitations of RECIST in measuring tumour shrinkage with local and systemic therapies, and also to refine the assessment of progression that could be misinterpreted with conventional RECIST 1.1, due to clinical events related to the natural progression of chronic liver disease (development of ascites, enlargement of lymph nodes, etc.). mRECIST has served its purpose since being adopted or included in clinical practice guidelines (European, American and Asian) for the management of HCC; it has also been instrumental for assessing response and time-to-event endpoints in several phase II and III investigations. Nowadays, mRECIST has become the standard tool for measurement of radiological endpoints at early/intermediate stages of HCC. At advanced stages, guidelines recommend both methods. mRECIST has been proven to capture higher objective response rates in tumours treated with molecular therapies and those responses have shown to be independently associated with better survival. With the advent of novel treatment approaches (i.e. immunotherapy) and combination therapies there is a need to further refine and clarify some concepts around the performance of mRECIST. Similarly, changes in the landscape of standard of care at advanced stages of the disease are pointing towards progression-free survival as a potential primary endpoint in some phase III investigations, as effective therapies applied beyond progression might mask overall survival results. Strict recommendations for adopting this endpoint have been reported. Overall, we review the performance of mRECIST during the last decade, incorporating novel clarifications and refinements in light of emerging challenges in the study and management of HCC.

Keratinocyte cancers – basal and cutaneous squamous cell carcinoma (BCC, cSCC) – are the most common forms of non-melanoma skin cancer (NMSC) and there has been a significant increase in their incidence globally in recent decades. Although the majority of BCC and cSCC are cured with conventional surgery or radiotherapy, certain tumour or patient-determined factors may result in these modalities being inadequate or inappropriate, for example, locally advanced or metastatic disease, high tumour multiplicity, patient comorbidities and patient preferences. In these clinical circumstances, systemic treatment may be indicated, and over the past 10 years a number of new systemic agents have been approved. Nonetheless, effective systemic therapy for keratinocyte cancers remains an area of significant unmet clinical need. Improved understanding of the molecular and immune pathogenesis underlying tumour growth and development is critical for driving future advances and is a research priority. The aim of this review is to provide clinicians with an overview of systemic treatments for BCC and cSCC and will focus on current evidence for conventional chemotherapy, targeted therapies, immunotherapy, adjuvant and neoadjuvant therapy, chemoprevention and future prospects for novel systemic treatment approaches.

Psoriasis impacts the quality of life (QoL) by disrupting overall health and social life. Thus, the use of a QoL evaluation item is crucial in assessing a therapeutic regimen. Also, faster improvements in QoL lead to better patient compliance, but very few studies compare psoriasis traditional and biologic therapies timing. To evaluate how much different systemic therapies improve disease severity and QoL, a retrospective analysis was performed on 56 patients. Subjects were administered different drugs and their vital statistics, psoriasis area severity index (PASI) and PSOdisk were collected at baseline and after 30 days. We found a moderate correlation between PASI and PSOdisk score with (r): .62. In terms of clinical scores improvement after 30 days, Ustekinumab turned out to be the fastest therapy available, while cyclosporine, among the systemic therapies available, appeared as highly competitive if not better than other biologic therapies.

Psoriasis is a chronic inflammatory condition. The age of onset, chronicity, physical, and psychosocial consequences of the disease cause psoriasis to have a significant impact on patient quality of life. Scalp psoriasis is no different, and effective treatment results in an improvement in quality of life. Successful management of scalp psoriasis includes topical therapies that are acceptable to the patient for mild-to-moderate disease, and systemic therapies for recalcitrant or moderate-to-severe disease. The most effective topical therapies are corticosteroid products, or combination products with calcipotriol and corticosteroid. Newer vehicle options provide more attractive and pleasing products for patients and may improve adherence. The current perspectives for management of scalp psoriasis are discussed including available data for systemic therapy of severe disease.

Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity. Some open problems still remain and different immunotherapy trials are underway, following promising preliminary results. In this review we analyze: the most recent advancements about patients treated with sorafenib; the results of RESORCE and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we discuss how they could address the current problems and possibly reshape the future of the systemic treatments for HCC.

Ertugrul Eryılmaz,1 Cengiz Canpolat2 1Department of Pediatrics, Division of Pediatric Hematology and Oncology, Acibadem Maslak Hospital, 2Department of Pediatric Hematology and Oncology, Acibadem Kozyatagi Hospital, Acibadem University School of Medicine, Istanbul, Turkey Abstract: Achieving lower morbidity and higher survival rates in the treatment of childhood leukemia has been a paradigm of success in modern oncology. However, serious long-term health complications occur in very large populations of childhood leukemia survivors, in the case of both acute lymphoid leukemia and acute myeloid leukemia (AML). Additionally, 15% of acute lymphoid leukemia patients have treatment failures, and rates are even higher in childhood AML. In the last few decades, as a result of well-tested experiments that statistically analyzed treatment cohorts, new agents have emerged as alternatives or supplements to established treatments, in which high survival and/or less morbidity were observed. This review provides an overview of better practice in the treatment of childhood leukemia. Keywords: acute lymphoblastic leukemia, acute myeloid leukemia, pediatric leukemia, systemic therapies&nbsp

Hepatocellular carcinoma (HCC) is the main cause of death in patients with cirrhosis, with an increasing incidence worldwide. Sorafenib is the choice therapy for advanced HCC. Over time several randomized phase III trials have been performed testing sunitinib, brivanib, linifanib and other molecules in head-to-head comparison with Sorafenib as first-line treatment for advanced-stage HCC, but none of these has so far been registered in this setting. Moreover, another feared vacuum arises from the absence of molecules registered as second-line therapy for patients who have failed Sorafenib, representing an urgent unmet medical need. To date all molecules tested as second-line therapies for advanced hepatocellular carcinoma, failed to demonstrate an increased survival compared to placebo. What are the possible reasons for the failure? What we should expect in the near future?

La evidencia en investigación de resultados en psicoterapia señala la relevancia de los factores comunes en el cambio terapéutico, los cuales dependen en buena medida de la participación y protagonismo del paciente. Los modelos de orientación post-estructuralista en psicoterapia sistémica promueven de forma directa y explícita los factores de cambio/comunes, como la alianza terapéutica, las expectativas y los factores extra-terapéuticos, permitiendo la acomodación, instancia relevante que otorga al consultante un rol decisivo para el cambio terapéutico. Los modelos posestructuralistas son buenas instancias formativas, en especial para la adquisición de destrezas que movilicen factores de cambio. The evidence in psychotherapy out come research points to the importance of the common factors in therapeutic change, which depend largely on patient participation. Models of post-structuralist orientation in systemic psychotherapy promote direct and explicitly change/common factors, as the therapeutic alliance, expectatives and extra-therapeutic factors, allowing the accommodation, relevant instance giving the consultant a decisive role for therapeutic change. The poststructuralist models are good instances formational, especially for the acquisition of skill stomobilize change factors.