Progress in Tumor Research最新文献

Target volume definition is of obvious importance in successful radiotherapy. Single-energy CT scans remain the standard, but FDG-PET-CT scans aid the determination of which lymph nodes should be included in the gross tumor volume and to fine-tune areas of cancer involvement. FDG-PET-CT imaging remains the gold standard in clinical practice. Hypoxia and proliferation tracers are still investigational, as is PET-guided redistribution of the radiation dose within the tumor. Contrast-enhanced CT as well as 4D CT scans contain information such as the characteristics of the lungs that are related to individual radiosensitivity, ventilation, and perfusion. Dual-energy CT imaging holds promise for the future for characterization of both tumor and normal tissues. The assessment of response after radiotherapy on the basis of CT scans remains difficult because of inflammatory and fibrotic changes. RECIST is still the standard. FDG avidity suffers from too high rates of false positive and false negative signals and is therefore not recommended, except on clinical indication.

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. The varying types of GCTs, defined by primary site and/or age at presentation, can look very similar microscopically. However, there is growing evidence that they may have different molecular characteristics, different biology and different requirements for curative treatments. Whilst in adult testicular GCTs there is evidence for an environmental cause during fetal development and a genetic component, these causative factors are much less well understood in other GCTs. GCTs are some of the most curable cancers in adults, but some patients exhibit resistance to standard treatments. Because of this, today's clinical research is directed at understanding how to best utilize toxic therapies and promote healthy survivorship. This chapter explores the biology, behavior and treatment of GCTs and discusses how the AYA group of GCTs may hold some of the keys to understanding fundamental unanswered questions of biological variance and curability in GCTs.

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. Age-related differences in tumor biology have been demonstrated mainly in DLBCL but there is still a need for biological studies to better understand age-related differences in this age group. AYA patients currently diagnosed with HL and NHL have 5-year survival expectations exceeding 90 and 75%, respectively. Different therapeutic strategies are often used in children and adult lymphoma and the dispersion of lymphoma care between adult and pediatric hematologist-oncologists results in heterogeneous strategies for each subgroup according to age. The impact of these different strategies on outcomes is not easy to evaluate given the paucity of population-based data focused on this age group, taking into account tumor biology and the lack of a uniform staging system. Given the excellent results obtained with current therapies, the challenge now is to develop strategies aimed at reducing acute and long-term toxicity in most patients while maintaining high cure rates and to identify patients at high risk of failure requiring new strategies including more selective targeted therapies.

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. We propose several strategies which could be applied to overcome these obstacles, some ready for implementation and others which require further exploration. Strengthening pediatric and adult oncology collaboration at the individual level and through oncology societies will undoubtedly positively impact accrual to trials for TYA, as will abolishing the use of age as a barrier to drug and trial access. This will allow us to create biologically driven trials and facilitate early new drug access and the creation of biobank collections to drive our understanding of the biology of cancers in this age group. Involving multiple stakeholders in trial design will facilitate acceptable trials to both healthcare professionals and young people themselves. The support of the multidisciplinary TYA team and a culture of research embedded within this are the keys to improving access and participation of TYA in cancer trials.

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. This chapter reviews the current status of epidemiology, pathophysiology, treatment strategies and outcomes of AYA leukemia, with a focus on acute lymphoblastic leukemia and acute myeloid leukemia.

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. The topics we include in the chapter are the following: the youth friendly environment, social support and social network, parents, information during a psychosocial crisis event, the use of HEADSS, peer support, fertility, body image and self-esteem, after treatment and future challenges and palliative and end of life care.

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. The relative improvement in the survival rate in AYAs has not kept pace with that achieved in younger children, especially for acute leukemia, non-HLs, Ewing tumors and rhabdomyosarcoma. Etiological factors are under-researched and remain largely hypothetical. In this unique group of illnesses, improving AYA cancer management involves bridging interfaces. Since this has begun, outcomes have also begun to improve. The local nature of these interfaces determines the age group considered as AYA. Specific skills are necessary in the clinical, biological and psychosocial domains. Services need support from policy, clinical and administrative professionals. National policy and supranational groups such as SIOPE and ESMO are in constructive collaboration to develop this further.

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. These tumors are less well understood, usually not managed according to standardized protocols and rarely included in clinical trials. Survival outcomes are generally poorer than their childhood equivalents. We present here a summary of the published literature on embryonal tumors that present ectopically during adolescence and adulthood. We show that for some tumors protocol-driven treatment, supported by accurate and complete diagnostics and staging, can result in equivalent outcomes to those seen during childhood. We make the case that clinical trial eligibility criteria should be disease-based rather than age-based, and support improvements in dialogue between children's and adults' cancer clinicians to improve outcomes for these rare tumors.