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While some recent drug treatments have been transformative for patients with cancer, many treatments offer small benefits despite high clinical toxicity, time toxicity and financial toxicity. Moreover, treatments that do provide substantial clinical benefits are not available to many patients globally due to issues with availability and affordability. The Common Sense Oncology's vision is that patients will have access to treatments that provide meaningful improvements in outcomes that matter, regardless of where they live. In recognition of the growing challenges in the field of oncology, Common Sense Oncology seeks to achieve this vision by improving evidence generation, evidence interpretation and evidence communication.
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Oncologia , Neoplasias , Humanos , Oncologia/economia , Neoplasias/terapia , Neoplasias/economia , Resultado do TratamentoRESUMO
PURPOSE: This study aims to (1) explore the prevalence of patient-reported financial difficulties among GIST patients, differentiating between those currently undergoing tyrosine kinase inhibitor (TKI) treatment and those who are not; (2) investigate associations between financial difficulties and sociodemographic and clinical characteristics, work, cancer-related concerns, anxiety and depression and (3) study the impact of financial difficulties on health-related quality of life. METHODS: A cross-sectional study was conducted among Dutch GIST patients diagnosed between 2008 and 2018, who were invited to complete a one-time survey between September 2020 and June 2021. Patients completed nine items of the EORTC item bank regarding financial difficulties, seven work-related questions, the Hospital Anxiety and Depression Scale, Cancer Worry Scale and EORTC QLQ-C30. RESULTS: In total, 328 GIST patients participated (response rate 63.0%), of which 110 (33.8%) were on TKI treatment. Patients currently treated with TKIs reported significantly more financial difficulties compared to patients not on TKIs (17.3% vs 8.7%, p = 0.03). The odds of experiencing financial difficulties was 18.9 (95% CI 1.7-214.7, p = 0.02) times higher in patients who were less able to work due to their GIST diagnosis. Patients who experienced financial difficulties had significantly lower global quality of life and functioning, and more frequently reported psychological symptoms as compared to patients who did not report financial difficulties. CONCLUSION: Even in a country where the costs of TKIs and follow-up care are covered by health insurance, financial difficulties can be present in GIST patients, especially in patients on TKI treatment, and may negatively influence the quality of life.
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Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/epidemiologia , Estudos Transversais , Qualidade de Vida , Países Baixos/epidemiologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Gastrointestinais/patologiaRESUMO
BACKGROUND: There are two main coping styles regarding information seeking under medical threat; monitoring (information-seeking) and blunting (information-avoiding). The aim of this study is to (1) determine factors associated with a monitoring or blunting coping style in gastro-intestinal stromal tumour (GIST) patients and (2) investigate its association with psychological distress, cancer-related concerns, health-related quality of life and satisfaction with healthcare. METHODS: In a cross-sectional study, Dutch GIST patients completed the shortened version of the Threatening Medical Situations Inventory to determine their coping style, the Hospital Anxiety and Depression Scale, Cancer Worry Scale, EORTC QLQ-C30 and part of the EORTC QLQ-INFO25. RESULTS: A total of 307 patients were classified as blunters (n = 175, 57%) or monitors (n = 132, 43%). Coping style was not associated with tumour or treatment variables, but being a female (OR 2.5; 95%CI 1.5-4.1; p= <.001) and higher educated (OR 5.5; 95%CI 2.5-11.9, p= <.001) were associated with higher odds of being a monitor. Monitors scored significantly lower on emotional functioning (mean = 86.8 vs mean = 90.9, p=.044), which is considered a trivial difference, more often experienced severe fear of cancer recurrence or progression (53.0% vs 37.7%, p=.007), and had more concerns about dying from GIST in the future (60.6% vs 47.4%, p=.025). Compared to blunters, monitors were less satisfied with the received healthcare and information, and would have liked to receive more information. CONCLUSION: GIST patients with a monitoring coping style experience a higher emotional burden. Additionally, monitors exhibit a greater need for information. Although this need for information could potentially result in fears and concerns, recognising it may also create an opening for tailored communication and information.
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Tumores do Estroma Gastrointestinal , Angústia Psicológica , Humanos , Feminino , Qualidade de Vida , Estudos Transversais , Satisfação do Paciente , Recidiva Local de Neoplasia , Adaptação Psicológica , Satisfação PessoalRESUMO
BACKGROUND: The patterns and determinants of long-term income among adolescent and young adult (AYA) cancer survivors, and the differences compared with peers, have not yet been fully explored. This study investigated the long-term effects of cancer on the income of AYA cancer survivors. METHODS: The Netherlands Cancer Registry identified all AYA cancer patients (aged 18-39 years) diagnosed in 2013 and alive 5 years postdiagnosis. Clinical data of the selected AYA patients were linked to individual, administrative real-world labor market data of Statistics Netherlands. The control group consisted of a random sample of individuals of the same age, sex, and migration background without cancer. Data on 2434 AYA cancer patients and 9736 controls were collected annually from 2011 until 2019. Changes in income level were measured and compared with the control group using difference-in-difference regression models. RESULTS: AYA cancer survivors experience, on average, an 8.5% decrease in annual earnings, relative to the control population. The effects are statistically significant and permanent (P < .01). Younger AYAs (those aged 18-25 years 15.5% income reduction), married cancer survivors (12.3%), females (11.6%), those diagnosed with stage IV disease (38.1%), and central nervous system (15.7%) cancer patients experienced the largest decline in income, on average, relative to controls, all else constant. CONCLUSION: Although dependent on the sociodemographic and clinical characteristics, a cancer diagnosis at AYA age has significant implications on the income of cancer patients. Awareness of vulnerable groups and the development of policies to mitigate the financial impact of cancer are critical.
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Sobreviventes de Câncer , Neoplasias , Feminino , Humanos , Adulto Jovem , Adolescente , Adulto , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Longitudinais , Sistema de Registros , Projetos de PesquisaRESUMO
Few studies describe supportive care needs among young adults (YAs) with cancer ages 25 to 39 using validated questionnaires. Previous findings identified the need for psychological and information support and suggest that gender, age, psychological distress, and coping may be associated with greater need for this support. To substantiate these findings, this study aimed to (1) describe the supportive care needs of YAs in each domain of the Supportive Care Needs Survey and (2) explore the relationship between unmet supportive care needs and clinical and demographic factors, health-related quality of life, psychological distress, illness cognitions, and service needs using latent class analysis. Clinical teams from six hospitals in England invited eligible patients to a cross-sectional survey by post. A total of 317 participants completed the survey online or on paper. YAs expressed the most need in the psychological and sexuality domains. Using latent class analysis, we identified three classes of YAs based on level of supportive care need: no need (53.3%), low need (28.3%), and moderate need (18.4%). In each class, median domain scores in each domain were similar. Low and moderate need classes were associated with worse health-related quality of life and greater helplessness. Unmet service needs were associated with the moderate-need class only. Patients with unmet supportive care needs should be offered holistic care across supportive care domains.
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Adolescent and young adult (AYA) cancer patients suffer from delay in diagnosis, and lack of centralized cancer care, age-adjusted expertise, and follow-up care. This group presents with a unique spectrum of cancers, distinct tumor biology, cancer risk factors, developmental challenges, and treatment regimens that differ from children and older adults. It is imperative for advances in the field of AYA oncology to pool data sources across institutions and create large cohorts to address the many pressing questions that remain unanswered in this vulnerable population. We will create a nationwide infrastructure (COMPRAYA) for research into the incidence, predictive/prognostic markers, and underlying mechanisms of medical and psychosocial outcomes for AYA between 18-39 years diagnosed with cancer. A prospective, observational cohort of (n = 4000), will be established. Patients will be asked to (1) complete patient-reported outcome measures; (2) donate a blood, hair, and stool samples (to obtain biochemical, hormonal, and inflammation parameters, and germline DNA); (3) give consent for use of routinely archived tumor tissue and clinical data extraction from medical records and registries; (4) have a clinic visit to assess vital parameters. Systematic and comprehensive collection of patient and tumor characteristics of AYA will support the development of evidence-based AYA care programs and guidelines.
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Historically, adolescent and young adult (AYA) patients with cancer, diagnosed for the first time at age 15 through 39 years, have often been identified as a "lost tribe" without a medical "home"; neither pediatric nor adult oncology services were able to provide age-appropriate care to this specific group. Internationally, AYA care programs are being established to bridge the gap between the age-defined healthcare worlds and to address the specific needs of AYAs with cancer. However, AYA care programs mostly focus on improving cure rates and addressing survivorship issues, and direct less attention to the unique needs of those living with an uncertain and/or poor cancer prognosis. Additionally, palliative care services are typically poorly equipped to address the age-specific needs of this group. Given that increasingly more AYAs with an uncertain and/or poor cancer prognosis are gaining life years because of novel treatments, and sometimes even face the prospect of long-term disease control, AYA care programs should address the unique palliative care needs of this "new" lost tribe within AYA oncology. This report provides a definition and description of the AYA population living with an uncertain and/or poor cancer prognosis in terms of epidemiologic, clinical, and psychosocial characteristics and challenges, and provides perspectives for future research and care initiatives. It also highlights the need to comprehensively examine the experience of AYAs who are living with uncertain and/or poor cancer prognosis to adjust best care practices for this unique group.
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Neoplasias , Adolescente , Adulto , Atenção à Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Cuidados Paliativos , Incerteza , Adulto JovemRESUMO
In the Netherlands, each year 2700 adolescents and young adults (AYA) aged 18 to 35 years are diagnosed with cancer. AYAs have age-specific problems in the areas of education, work, relationships and children that require specific attention. In 2013, we set up the Dutch national AYA 'Youth and Cancer' [Jong & Kanker] platform in co-creation between AYAs and healthcare professionals to address these problems. In this article we discuss the status and future perspectives of this platform.
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Acessibilidade aos Serviços de Saúde/organização & administração , Necessidades e Demandas de Serviços de Saúde/organização & administração , Neoplasias/terapia , Equipe de Assistência ao Paciente/organização & administração , Adolescente , Feminino , Pessoal de Saúde/organização & administração , Humanos , Masculino , Avaliação das Necessidades , Países Baixos , Adulto JovemRESUMO
Trabectedin and ifosfamide are among the few cytostatic agents active in advanced soft tissue sarcomas (STSs). Trabectedin is most potent against so-called L-sarcomas (leiomyosarcoma and liposarcoma). The survival gain and cost-effectiveness of these agents in a second-line setting were analysed in the setting of advanced STS after failure of anthracyclines. A prospective observational trial had previously been performed to assess the use of trabectedin in a Dutch real-world setting. Data on ifosfamide monotherapy were acquired from previous studies, and an indirect comparison of survival was made. A state-transition economic model was constructed, in which patients could be in mutually exclusive states of being preprogression, postprogression, or deceased. The costs and quality-adjusted life years (QALYs) for both treatments were assessed from a Dutch health-care perspective. Separate analyses for the group of L-sarcomas and non-L-sarcomas were performed. Trabectedin treatment resulted in a median progression-free survival of 5.2 months for L-sarcoma patients, 2.0 months for non-L-sarcoma patients, and a median overall survival of 11.8 and 6.0 months, respectively. For L-sarcoma patients, trabectedin offered an increase of 0.368 life years and 0.251 QALYs compared to ifosfamide and 20,082 in additional costs, for an incremental cost-effectiveness ratio (ICER) of 80,000 per QALY gained. In the non-L-sarcoma patients, trabectedin resulted in 0.413 less life years and 0.266 less QALYs, at the increased cost of 4,698. The difference in survival between drugs and the acquisition costs of trabectedin were the main influences in these models. Trabectedin was shown to have antitumour efficacy in advanced L-sarcoma. From a health economics perspective, the costs per QALY gained compared to ifosfamide monotherapy that may be acceptable, considering what is currently regarded as acceptable in the Netherlands.
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BACKGROUND: Platinum-based chemoradiotherapy for locally advanced head and neck cancer (LAHNC) induces a high rate of acute toxicity, including dysphagia and aspiration pneumonia. We hypothesised that prophylactic antibiotics can prevent pneumonia and hospitalisations and can be cost-effective. PATIENT AND METHODS: In this multicentre randomised trial, patients with LAHNC treated with chemoradiotherapy received prophylactic amoxicillin/clavulanic acid from day 29 after the start of treatment until 14 days after completion of chemoradiotherapy or standard care without prophylaxis. The primary objective was to observe a reduction in pneumonias. Secondary objectives were to evaluate the hospitalisation rate, adverse events, costs and health-related quality of life. RESULTS: One hundred six patients were included; of which, 95 were randomised: 48 patients were allocated to the standard group and 47 patients to the prophylaxis group. A pneumonia during chemoradiotherapy and follow-up until 3.5 months was observed in 22 (45.8%) of 48 patients in the standard group and in 22 (46.8%) of 47 patients in the prophylaxis group (p = 0.54). Hospitalisation rate was significantly higher in the standard group versus the prophylaxis group, 19 of 48 pts (39.6%) versus 9 of 47 pts (19.1%), respectively (p = 0.03). Significantly more episodes with fever of any grade were observed in the standard group (29.2% vs 10.2%, p = 0.028). A significant difference in costs was found, with an average reduction of 1425 per patient in favour of the prophylaxis group. CONCLUSION: Although prophylactic antibiotics during chemoradiotherapy for patients with LAHNC did not reduce the incidence of pneumonias, it did reduce hospitalisation rates and episodes with fever significantly and consequently tended to be cost-effective.
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Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Carcinoma/terapia , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Custos de Cuidados de Saúde , Hospitalização/estatística & dados numéricos , Pneumonia/prevenção & controle , Adulto , Idoso , Antibioticoprofilaxia , Antineoplásicos/efeitos adversos , Carcinoma/patologia , Cisplatino/efeitos adversos , Análise Custo-Benefício , Transtornos de Deglutição/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Mucosite/etiologia , Pneumonia/etiologia , Qualidade de Vida , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto JovemRESUMO
PURPOSE: Sporadic desmoid-type fibromatosis (DTF) is a rare, chronic, non-metastasising, disease of the soft tissues. It is characterised by local invasive and unpredictable growth behaviour and a high propensity of local recurrence after surgery thereby often having a great impact on health-related quality of life (HRQL). This study aims to review currently used HRQL measures and to asses HRQL issues among DTF patients. METHODS: A mixed methods methodology was used consisting of (1) a systematic literature review, according to the PRISMA guidelines (2009), using search terms related to sporadic DTF and HRQL in commonly used databases (e.g. Embase, Medline Ovid, Web of science, Cochrane Central, Psyc Info, and Google scholar), to provide an overview of measures previously used to evaluate HRQL among DTF patients; (2) focus groups to gain insight into HRQL issues experienced by DTF patients. RESULTS: The search strategy identified thirteen articles reporting HRQL measures using a wide variety of cancer-specific HRQL tools, functional scores, symptom scales (e.g. NRS), and single-item outcomes (e.g. pain and functional impairment). No DTF-specific HRQL tool was found. Qualitative analysis of three focus groups (6 males, 9 females) showed that participants emphasised the negative impact of DTF and/or its treatment on several HRQL domains. Six themes were identified: (1) diagnosis, (2) treatment, (3) follow-up and recurrence, (4) physical domain, (5) psychological and emotional domain, and (6) social domain. CONCLUSION: A DTF-specific HRQL tool and consensus regarding the preferred measurement tool among DTF patients is lacking. Our study indicates that HRQL of DTF patients was negatively affected in several domains. A DTF-specific HRQL measure could improve our understanding of short- and long-term effects and, ideally, can be used in both clinic and for research purposes.
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Fibromatose Agressiva/psicologia , Qualidade de Vida/psicologia , Adulto , Feminino , Fibromatose Agressiva/patologia , Grupos Focais , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: There is increasing recognition of the delicate balance between the modest benefits of palliative chemotherapy and the burden of treatment. Decision aids (DAs) can potentially help patients with advanced cancer with these difficult treatment decisions, but providing detailed information could have an adverse impact on patients' well-being. The objective of this randomised phase II study was to evaluate the safety and efficacy of DAs for patients with advanced cancer considering second-line chemotherapy. METHODS: Patients with advanced breast or colorectal cancer considering second-line treatment were randomly assigned to usual care (control group) or usual care plus a DA (intervention group) in a 1:2 ratio. A nurse offered a DA with information on adverse events, tumour response and survival. Outcome measures included patient-reported well-being (primary outcome: anxiety) and quality of the decision-making process and the resulting choice. RESULTS: Of 128 patients randomised, 45 were assigned to the control group and 83 to the intervention group. Median age was 62 years (range 32-81), 63% were female, and 73% had colorectal cancer. The large majority of patients preferred treatment with chemotherapy (87%) and subsequently commenced treatment with chemotherapy (86%). No adverse impact on patients' well-being was found and nurses reported that consultations in which the DAs were offered went well. Being offered the DA was associated with stronger treatment preferences (3.0 vs. 2.5; p=0.030) and increased subjective knowledge (6.7 vs. 6.3; p=0.022). Objective knowledge, risk perception and perceived involvement were comparable between the groups. CONCLUSIONS: DAs containing detailed risk information on second-line palliative treatment could be delivered to patients with advanced cancer without having an adverse impact on patient well-being. Surprisingly, the DAs only marginally improved the quality of the decision-making process. The effectiveness of DAs for palliative treatment decisions needs further exploration. TRIAL REGISTRATION: Netherlands Trial Registry (NTR): NTR1113 (registered on 2 November 2007).
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Técnicas de Apoio para a Decisão , Neoplasias/tratamento farmacológico , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Efeitos Psicossociais da Doença , Tomada de Decisões , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The difficulties adolescents and young adults (AYAs) encounter during a cancer experience may result in a reduction in or absence of empowerment. The aims of the current study were to assess levels of empowerment and associated (demographic, clinical, or psychological) factors and examine the association between empowerment and health-related quality of life (HRQOL) among AYA patients with cancer. METHODS: Patients aged 18 to 35 years at time of cancer diagnosis and who were seen by 1 of the members of the specialized multidisciplinary AYA team of the Radboud University Medical Center were invited to complete questionnaires regarding empowerment; HRQOL; and sociodemographic, clinical, and psychological characteristics (autonomy, coping, unmet social support needs, and psychological distress). RESULTS: A total of 83 AYA patients completed the questionnaires. The mean age of the participants at the time of diagnosis was 27.5 years. The vast majority had been treated with chemotherapy (86%), had a more advanced stage of disease, and had completed treatment at the time of participation (74%). The mean empowerment level was 154.1 (standard deviation, 17.8) with a range of 114 to 200. Multivariate analysis demonstrated that the autonomy subscales of self-awareness (ß = .35), capacity for managing new situations (ß = .19), and social support (ß = .35) were found to be positively associated with empowerment. Coping difficulties (ß = -.19) were found to be negatively associated with empowerment. Empowerment was independently associated with physical (ß = .31), psychological (ß = .50), social (ß = .39), religious (ß = .33), and total HRQOL (ß = .52; all P<.01). CONCLUSIONS: Low levels of empowerment were associated with low levels of autonomy and social support, female sex, and coping difficulties among AYA patients with cancer. Recognizing these patients as candidates for empowerment interventions ultimately could help to improve HRQOL in late adolescence and young adulthood. Cancer 2017;123:4039-47. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Nível de Saúde , Neoplasias/psicologia , Participação do Paciente/psicologia , Poder Psicológico , Qualidade de Vida/psicologia , Adaptação Psicológica , Adolescente , Adulto , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias/patologia , Neoplasias/terapia , Autonomia Pessoal , Apoio Social , Estresse Psicológico , Inquéritos e Questionários , Adulto JovemRESUMO
For solid tumours, quantitative analysis of [(18)F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography potentially can have significant value in early response assessment and thereby discrimination between responders and non-responders at an early stage of treatment. Standardised strategies for this analysis have been proposed, and the positron emission tomography response criteria in solid tumours (PERCIST) criteria can be regarded as the current standard to perform quantitative analysis in a research setting, yet is not implemented in daily practice. However, several exceptions and limitations limit the feasibility of PERCIST criteria. In this article, we point out dilemmas that arise when applying proposed criteria like PERCIST on an expansive set of patients with metastasised solid tumours. Clinicians and scientists should be aware of these limitations to prevent that methodological issues impede successful introduction of research data into clinical practice. Therefore, to deliver on the high potential of quantitative imaging, consensus should be reached on a standardised, feasible and clinically useful analysis methodology. This methodology should be applicable in the majority of patients, tumour types and treatments.
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Fluordesoxiglucose F18/farmacocinética , Imagem Multimodal/métodos , Neoplasias/diagnóstico , Neoplasias/terapia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada por Raios X , Humanos , Metástase Neoplásica , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Neoplasias/patologia , Valor Preditivo dos Testes , Interpretação de Imagem Radiográfica Assistida por Computador , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
The blood-brain barrier (BBB) is a functional barrier that hampers the delivery of various drugs to the brain by its physicoanatomical properties and by the presence of ATP-driven drug efflux pumps, such as P-glycoprotein (P-gp). The aims of this study were (1) to study whether the distribution volume (DV) is useful for quantification of (labeled) P-gp substrate kinetics over the BBB and (2) to study how brain DV is affected by P-gp modulation. We measured the kinetics of the P-gp substrate [11C]verapamil (0.1 mg/kg) in rat brains using positron emission tomography (PET) and arterial blood sampling. Cyclosporin A (CsA) at 0, 10, 15, 25, 35, and 50 mg/kg of body weight was used as a P-gp modulator. The [11C]verapamil kinetics were very well described by DV, computed by noncompartmental Logan analysis. Logan analysis resulted in excellent fits of dynamic PET data, revealing the reversible behavior of [11C]verapamil and its associated DV. The DV in unmodulated rats was 0.65 ml/ml +/- 0.23 (mean +/- SD). After modulation with 10, 15, 25, 35, and 50 mg/kg of CsA, DV values increased to 0.82 +/- 0.06, 1.04 +/- 0.20, 2.85 +/- 0.51, 2.91 +/- 0.64, and 3.77 +/- 1.23, respectively. The [11C]Verapamil kinetics were saturable at modulation levels above 25 mg/kg of CsA. The data fitted well by a four-parameter Hill plot (R2 = 0.79). In conclusion, the DV of [11C]verapamil is a valid and potent tool to measure the kinetics of (labeled) P-gp substrates in vivo at the BBB. The brain DV of [11C]verapamil increases dose dependently by P-gp modulation. Quantitative insight into in vivo P-gp modulation may be a promising step toward assessment of P-gp substrate delivery to human brains.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Barreira Hematoencefálica/fisiologia , Química Encefálica/fisiologia , Encéfalo/diagnóstico por imagem , Bloqueadores dos Canais de Cálcio , Compostos Radiofarmacêuticos , Verapamil , Animais , Radioisótopos de Carbono , Circulação Cerebrovascular/fisiologia , Modelos Neurológicos , Ratos , Ratos Wistar , Tomografia Computadorizada de EmissãoRESUMO
PURPOSE: Postradiation sarcoma, a sarcoma developing in a previously irradiated field, is a rare tumor. Surgery appears to be the only curative treatment option. In general the prognosis is poor, and new treatments options are needed. One study reported the expression of KIT receptor tyrosine kinase in two postradiation angiosarcomas. Success of inhibition of KIT in malignant gastrointestinal stromal tumors with imatinib mesylate seems mutation-dependent, with a favorable response in the presence of exon 11 mutations. EXPERIMENTAL DESIGN: We performed a clinical, immunohistochemical, and genetic assessment of postradiation sarcomas, including angiosarcomas. Archival tumor tissue was available from 16 patients diagnosed with a postradiation sarcoma between 1978 and 2001. Data on the first and secondary tumor, treatment, and follow-up was documented. KIT expression was assessed by immunohistochemistry. For comparison, 23 spontaneous soft tissue sarcomas of similar histological types were analyzed. Exon 11 of the c-kit gene was analyzed by direct DNA sequencing. RESULTS: Fifteen patients received initial irradiation for malignant disease and 1 patient for a benign condition. The median delivered dose was 50 Gy. The median latency period between irradiation and diagnosis of postradiation sarcomas was 222 months. Histological types included: angiosarcoma, fibrosarcoma, malignant fibrous histiocytoma, osteosarcoma, rhabdomyosarcoma, and unspecified sarcoma. In concordance with the literature, patients had a poor outcome. Only 3 of 16 patients were disease-free 43, 60, and 161 months after being diagnosed of postradiation sarcoma, all 3 having favorable tumor and treatment characteristics. Fourteen of 16 tumor samples were KIT-positive (88%). In 8 cases >80% of tumor cells stained positively. Five of 23 (22%) spontaneous soft tissue sarcomas of comparable histological types, including 2 angiosarcomas, were KIT-positive. Molecular genetic analysis of exon 11 of the c-kit gene was attainable for 13 of the 16 postradiation sarcomas. No mutations were found. CONCLUSIONS: Postradiation sarcomas are aggressive malignancies, seldom amenable to curative treatment. A majority of the analyzed tumors showed extensive expression of the KIT protein, but no mutations in exon 11 of the c-kit gene were found. Still, without the availability of effective therapies, treatment with the KIT inhibitor imatinib mesylate might be considered for patients with postradiation sarcomas.
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Neoplasias Induzidas por Radiação/diagnóstico , Proteínas Proto-Oncogênicas c-kit/metabolismo , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adolescente , Adulto , Idoso , Relação Dose-Resposta à Radiação , Éxons , Feminino , Hemangiossarcoma/enzimologia , Humanos , Imuno-Histoquímica , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Radioterapia/efeitos adversos , Sarcoma/enzimologia , Neoplasias de Tecidos Moles/enzimologia , Fatores de TempoRESUMO
The purpose of this study of treated Buruli ulcer patients in Ghana was to identify and assess late sequelae of treated Buruli ulcer using a goniometer, and to develop a scoring system for functional limitations. Of 78 patients, 58% (n = 45) had a reduction in the range of motion of one or more joints: 30% (n = 23) had one or more functional limitations of the leg and 21% (n = 16) of the arm; 49% (n = 38) had a functional limitation. Of all patients with affected knees, the predicted average extent of limitation was 63%. In patients with affected ankles, limitation was 78% on average; in those with elbow involvement, this was 76% on average, and in wrists involved, 65%. All of the hands involved were markedly restricted. We propose a simplified and functional scoring system that should be tested for validation in a second patient sample, and, if properly validated and adjusted, can be used in future intervention trials.