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Progress in Tumor Research

Andrea Ferrari, Uta Dirksen, Stefan Bielack
The definition of soft tissue and bone sarcomas include a large group of several heterogeneous subtypes of mesenchymal origin that may occur at any age. Among the different sarcomas, rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma and osteosarcoma are aggressive high-grade malignancies that often arise in adolescents and young adults. Managing these malignancies in patients in this age bracket poses various clinical problems, also because different therapeutic approaches are sometimes adopted by pediatric and adult oncologists, even though they are dealing with the same condition...
2016: Progress in Tumor Research
Gabriele Calaminus, Jonathan Joffe
Germ cell tumors (GCTs) represent a group of biologically complex malignancies that affect patients at different sites within the body and at different ages. The varying nature of these tumors reflects their cell of origin which is the primordial germ cell, which normally gives rise to ovarian and testicular egg and sperm producing cells. These cells retain an ability to give rise to all types of human tissues, and this is illustrated by the different kinds of GCTs that occur. In adolescent and young adult (AYA) patients, GCTs predominantly present as testicular, ovarian or mediastinal primary GCTs, and represent some of the most complex therapeutic challenges within any AYA practice...
2016: Progress in Tumor Research
Laurence Brugières, Pauline Brice
Lymphomas are one of the commonest malignancies in adolescents and young adults (AYA) accounting respectively for 22% of all cancers in patients aged 15-24 years (16% for Hodgkin lymphoma (HL) and 6% for non-HL (NHL)). The distribution of NHL subtypes in this age group differs strikingly from the distribution in children and in older adults with 4 main subtypes accounting for the majority of the cases: diffuse large B-cell lymphoma (DLBCL) including primary mediastinal B-cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma or anaplastic large cell lymphoma...
2016: Progress in Tumor Research
Gunnar Juliusson, Rachael Hough
Leukemias are a group of life threatening malignant disorders of the blood and bone marrow. In the adolescent and young adult (AYA) population, the acute leukemias are most prevalent, with chronic myeloid leukemia being infrequently seen. Factors associated with more aggressive disease biology tend to increase in frequency with increasing age, whilst tolerability of treatment strategies decreases. There are also challenges regarding the effective delivery of therapy specific to the AYA group, consequences on the unique psychosocial needs of this age group, including compliance...
2016: Progress in Tumor Research
Martin G McCabe, Dominique Valteau-Couanet
Embryonal tumors classically occur in young children, some principally within the first year of life. Prospective national and international clinical trials during recent decades have brought about progressive improvements in survival, and associated biological studies have advanced our understanding of tumor biology, in some cases allowing biological tumor characteristics to be harnessed for therapeutic benefit. Embryonal tumors continue to occur, albeit less commonly, during childhood, adolescence and throughout adulthood...
2016: Progress in Tumor Research
Valérie Laurence, Maria Marples, Daniel P Stark
The pattern of cancer seen in young people changes with increasing age, transitioning from childhood- to adult-type cancer in adolescence and the third decade. The risk factors, presentation and biology of cancer in young adults differ from those in the older adult population. Factors of particular significance in adolescents and young adults (AYAs) include genetic predisposition to adult-type cancer, diagnostic uncertainty, long-term morbidity and considerations of fertility. New systemic therapies are being introduced that can prolong life and even increase the chance of cure, but the impact on AYAs is uncertain, as these patients are often under-represented in clinical trials...
2016: Progress in Tumor Research
O Husson, E Manten-Horst, W T A van der Graaf
Awareness of the need for collaboration across pediatric and adult cancer to care for adolescents and young adults (AYAs) arose from the recognition of the unique characteristics of AYAs with cancer. Neither pediatric nor adult oncology hospital departments are able to provide age-appropriate care single handedly. The best way to bridge the gap in care of AYA cancer patients is to centralize aspects of their care within dedicated AYA care programs, including the following essential components: provision of developmentally appropriate and multidisciplinary (supportive) care, availability of AYA inpatient and outpatient facilities and healthcare professional AYA expertise as collaboration between adult and pediatric departments...
2016: Progress in Tumor Research
Nathalie Gaspar, Lorna Fern
The inclusion of teenagers and young adults (TYAs) in cancer clinical trials is focal point for many countries with a specific TYA program. This objective has arisen from data which suggests that lower trial entry may, in part, contribute to lesser survival gains observed in this group when compared to children and some older adult cancers. In this chapter, we discuss obstacles to clinical trials and innovative therapies for TYA. Limited clinical trial availability is discussed in the context of the rarity of TYA cancers and our limited understanding of cancer biology in this group, other obstacles include inappropriate age eligibility criteria, limited accessibility to available trials, a lack of physicians and patients awareness and poor acceptability of trial design...
2016: Progress in Tumor Research
Aimilia Tsirou, Lars Hjorth
Within this chapter, we begin with the invaluable context of the experience of living after cancer as a young person. Then we move to describe the growing body of data indicating the consequences of cancer in patients diagnosed aged as teenagers and young adults (YAs). We identify that, while the variation in definitions used in the literature hamper firm conclusions, specific patterns of substantial morbidity are observed which are distinct from those seen in younger children. When combined with the epidemiology, the overall burden of late effects of adolescents and YA cancer and its treatment are a substantial public health problem...
2016: Progress in Tumor Research
Pia Riis Olsen, Rosalía Lorenzo
This chapter takes its point of departure in psychosocial aspects of supportive care in adolescent and young adult cancer care. The purpose is to describe some of the challenges that these young people face following a cancer diagnosis and guide healthcare professionals in how to provide care that improves the quality of life. In most hospitals and healthcare systems, adolescents and young adults are cared for and treated in settings for children or adults. Accordingly, healthcare professionals may lack attention to and knowledge about what characterize young peoples' life situation, their special needs and how to meet them...
2016: Progress in Tumor Research
Emmanuel Desandes, Daniel P Stark
To design the services for adolescents and young adults (AYAs) with cancer, we need to understand the patterns of disease and the other clinical and managerial challenges of the patient group. Cancer occurring between the ages of 15 and 39 years is 4 times less rare than cancer occurring during the first 15 years of life and consists of 2% of all invasive cancer in Europe, about 66,000 patients in Europe each year. AYAs have a unique distribution of cancer types, including the peak in incidence of Hodgkin lymphoma (HL) or germ cell tumors...
2016: Progress in Tumor Research
Niels Reinmuth, Martin Reck
Immunotherapy of cancer encompasses different strategies that elicit or enhance the immune response against tumors. The first results from clinical studies have provided promising data for the treatment of lung cancer patients with immunomodulating monotherapies. To improve the potential benefit of cancer immunotherapy, synergistic combinations of the various immunotherapy approaches or of different elements within each of the immunotherapy approaches are being explored. The rationale typically involves different but complementary mechanisms of action, eventually impinging on more than one immune system mechanism...
2015: Progress in Tumor Research
Kobe Reynders, Dirk De Ruysscher
Radiotherapy is an important cornerstone in cancer treatment. Ionizing gamma-irradiation is capable of inducing DNA damage and consequential cell death in a precise and effective manner. In recent years it has become clear, however, that this is not the only relevant mechanism of action. Radiotherapy alters the immune composition of the tumor and influences upregulation of MHC I and cancer-testis antigens, inducing immunogenic cell death and supporting dendritic cell activation. Paradoxically, it also increases the relative ratio of regulatory T cells to CD4+ cells, which hampers an effective immune response...
2015: Progress in Tumor Research
Mustafa Diken, Sebastian Kreiter, Björn Kloke, Ugur Sahin
Developments in sequencing technologies have not only led to a rapid generation of genomic and transcriptional data from cancer patients, but also revealed the vast diversity of cancer-specific changes in patient tumors. Among these, mutation changes in the protein sequence can result in novel epitopes recognized by the immune system and, therefore, can be employed in the development of personalized vaccines. Thanks to its easy design and scalable GMP production, vaccines based on mRNAs coding for mutated epitopes have emerged as a reliable strategy for the exploitation of the potential of patient-specific genomic data...
2015: Progress in Tumor Research
Magdalena Pircher, Thomas Schirrmann, Ulf Petrausch
T cells are a new and promising antigen-specific therapeutic option for the treatment of malignant diseases. To achieve antigen specificity against tumor antigens, T cells can be manipulated by gene transfer to express chimeric antigen receptors (CARs). CAR-expressing T cells are called redirected T cells. CARs are composed of an extracellular antibody-derived antigen recognition domain, a transmembrane domain and a cytoplasmatic signal domain. Therefore, redirected T cells combine the exchangeable specificity of an antibody with the cytotoxic machinery of a T cell...
2015: Progress in Tumor Research
Anil Shanker, Mikhail M Dikov, David P Carbone
Metastatic lung cancer is the most common cause of cancer mortality globally in both men and women, with 5-year survival of less than 5%. Standard treatment approaches for metastatic lung cancer are based on chemotherapy, with radiation and surgery used for local control, but these rarely result in relapse-free survivals longer than 2-3 years, although they may provide symptom relief. Thus, additional tools are needed to treat this disease. In this chapter, we discuss the various immune-based cancer treatments for lung cancer patients that are being developed, and the increasing awareness that therapies targeted at overcoming immune evasion mechanisms may be essential to clinical efficacy...
2015: Progress in Tumor Research
John B A G Haanen, Caroline Robert
Undoubtedly the discovery of immune checkpoints such as CTLA-4 and PD-1 has been crucial to the development of cancer immunotherapy. Although these molecules were originally discovered as molecules playing a role in T cell activation or apoptosis, subsequent preclinical research showed their important role in the maintenance of peripheral immune tolerance. Mice deficient of the immune checkpoints CTLA-4 or PD-1 develop autoimmune-like diseases that occur early after birth and are lethal in the case of CTLA-4 deficiency, or become apparent much later in life in the case of PD-1 deficiency...
2015: Progress in Tumor Research
Carmen Criscitiello, Giuseppe Curigliano
Cancer immunoediting is the process by which the immune system protects the host from tumor development and guides the somatic evolution of tumors by eliminating highly immunogenic tumor cells. A fundamental dogma of tumor immunology and of cancer immunosurveillance in particular is that cancer cells express antigens that differentiate them from their nontransformed counterparts. Molecular studies clearly show that these antigens were often products of mutated cellular genes, aberrantly expressed normal genes, or genes encoding viral proteins...
2015: Progress in Tumor Research
Alexandra Snyder, Dmitriy Zamarin, Jedd D Wolchok
The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1...
2015: Progress in Tumor Research
Benjamin Kasenda, James Larkin, Martin Gore
The development of new immunomodulatory monoclonal antibodies targeting the CTLA-4 or PD-1 axis has led to a revival of research on immunotherapies in solid tumours including renal cell cancer (RCC). The initial results observed with these monoclonal antibodies in the treatment of advanced melanoma have resulted in considerable interest in this treatment strategy in all tumour types. Preliminary data of these new antibodies in advanced RCC are promising and they have good safety profiles. Response rates are low but durable tumour control has been observed in some patients...
2015: Progress in Tumor Research
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