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INTRODUCTION: Despite the benefits of quitting smoking for those who have cancer, including improved health outcomes and reduced therapeutic toxicities, it is unclear how many people are supported in quit attempts during this time. Variations in the availability and provision of smoking cessation (SC) services are reported, with little understanding of the challenges and solutions. This co-designed study aimed to understand the perspectives of health care professionals (HCPs) working in oncology settings to engage in SC practices and identify recommendations for developing an SC pathway. METHODS: This was a qualitative study. Eighteen HCPs participated in semi-structured interviews from July 2021 to May 2022. We used thematic analysis approaches to code data and present four emergent themes and SC strategies at micro, meso and organizational levels. RESULTS: Four themes emerged specifically: 1) timing and knowledge, 2) building a relationship, 3) frequent asking with infrequent action, and 4) removing the barriers and tailoring the system. While HCPs discuss SC, there are variations in documentation and when conversations occur. Primarily, HCPs value the time to build therapeutic relationships with patients and thus may limit SC discussions in preference to treatment in clinical interactions. The role of structural barriers, including prescriptive authority for nurses, hinders active SC processes, as it is the lack of continuity and embedding of services supported by a clinical champion for SC. CONCLUSIONS: The study suggests re-evaluating the status quo in SC service, highlighting service gaps and suggesting opportunities at organizational levels to reduce structural barriers. IMPLICATIONS: Variations in smoking cessation services exist in designated cancer centres. The data from this study can be used to inform a real time health systems approach for SC services in oncology settings. Developing tailored smoking cessation services and interventions that are patient-centred and informed by their experiences are required. The data in this study suggests developing specialist education and training to upskill HCPs for equitable engagement if we are to meet EU and Moonshot goals for cancer reduction.
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Background: Facemasks accurately immobilise patients with head and neck cancer (HNC) receiving radiotherapy (RT). However, such masks are associated with treatment related distress, a prognostic factor for poorer survival. Open masks offer increased comfort and patient satisfaction. We investigated whether open masks could immobilise patients without affecting treatment accuracy. Materials and methods: Over an 18-month period, all HNC RT patients with anxiety were offered open masks. Once 30 patients had completed treatment, set-up data was compared to patients in closed masks. The mean displacement and one-dimensional standard deviations (SD) of the mean, systematic and random set-up errors were calculated for translational directions: anterior-posterior (x), superior-inferior (y), medial-lateral (z). The mean and SD of the mean was calculated for rotational displacements. Mann-Whitney U was used to determine any significant differences between set-up data. Results: Sixty patients were included (30 open & 30 closed masks). There was no statistically significant difference found in the x (p = 0.701), y (p = 0.246) or z (p = 0.535) direction for the SD of the mean displacements between both masks. No statistically significant difference was found in the SD of means for rotational displacements. The calculated planning target volume (PTV) margin requirements were minimally less for the closed masks 3.5, 2.6, and 2.7 mm (x, y, z, respectively) versus 4.2, 3.2, and 3.7 mm, respectively, for open masks. Conclusion: Our study demonstrates that open masks maintain accuracy at levels comparable to closed masks in patients with anxiety. The minor difference in the calculated PTV margin could be rectified with daily on-line imaging or surface guided imaging.
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BACKGROUND: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. METHODS: We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. FINDINGS: Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007). INTERPRETATION: Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. FUNDING: Cancer Research UK.
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Antineoplásicos/uso terapêutico , Cetuximab/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Doença Aguda , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Medição de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Resultado do TratamentoRESUMO
AIM: To explore the effectiveness and feasibility of implementing the two clinical dimensions of the Careful Nursing Philosophy and Professional Practice Model© (Careful Nursing) in an acute care hospital. BACKGROUND: Implementation of a professional practice model by nurses in hospitals supports nurses' control over their practice and enhances the quality of their contribution to patient care. Implementing such change is complex and initially best approached on a small scale. METHODS: A mixed methods exploratory design was used. Data were sought from 23 professional nurses practising in a 26-bed acute medical ward for older persons. Quantitative data were collected on nurses' control over and documentation of their practice. Qualitative data were collected on nurses' perceptions of their practice. RESULT: Nurses' control over practice and adherence to practice documentation standards increased. Overall, the nurses perceived Careful Nursing-guided practice positively. Feasibility issues were identified and addressed. CONCLUSION: Exploratory evidence suggests that Careful Nursing could influence nurses' practice and overall perception of practice positively; its implementation is feasible. IMPLICATIONS FOR NURSING MANAGEMENT: Careful Nursing offers a distinctive nursing framework for professional practice. This study can provide a strategy for implementing Careful Nursing-guided changes in hospital-based practice on an exploratory level.
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Educação/normas , Modelos de Enfermagem , Papel Profissional , Desenvolvimento de Programas/métodos , Adulto , Atitude do Pessoal de Saúde , Educação/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
AIM: The aim of this research is to establish if variation exists in the dose delivered for head and neck (HN) localisation computed tomography (CT) imaging in radiation therapy (RT); to propose a national diagnostic reference levels (DRLs) for this procedure and to make a comparison between the national DRL and a DRL of a European sample. BACKGROUND: CT has become an indispensable tool in radiotherapy (RT) treatment planning. It is a requirement of legislation in many countries that doses of ionising radiation for medical exposures be kept 'As Low As Reasonably Achievable'. There are currently no dose guidelines for RT localisation CT of the HN. MATERIALS AND METHODS: All RT departments in Ireland and a sample of European departments were surveyed. Dose data on CT dose length product (DLP); dose index volume (CTDIvol); current time product; tube voltage and scan length was acquired for ten average-sized HN patients from each department. DRLs were proposed for DLP and CTDIvol using the rounded 75th percentile of the distribution of the means. RESULTS: 42% of Irish departments and one European department completed the survey. Significant variation was found in the mean DLP, CTDIvol and scan lengths across the Irish departments. The proposed Irish DRL is 882 mGy cm and 21 mGy and the European department DRL is 816 mGy cm and 21 mGy, for DLP and CTDIvol, respectively. CONCLUSIONS: Variation exists in doses used for HN RT localisation CT. DRLs have been proposed for comparison purposes with the aim of dose optimisation.
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Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted standard of care in head and neck squamous cell carcinoma. However, this regimen is associated with severe toxicities with devastating effects on patients. Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce toxicities. The main objective of the present study is to identify the dose intensities and toxicities of weekly cisplatin in patients treated in a tertiary centre over a 12 month period. Included patients had squamous cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis or if they had prior treatment for head and neck cancer excluding neck dissection. During the study period, 52 patients met the inclusion criteria and their data were retrospectively obtained from the patients' database of St James hospital, Dublin. The median age of the study cohort was 54 years (range 33-73). Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in 10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in 35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37 (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis, which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4 neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively. The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %) patients. There was no grade 3 or 4 renal toxicity among the study cohort, although grade 2 was observed in six (11.5 %) patients. Death occurred in one patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is associated with moderate to severe toxicities and might lead to suboptimal chemotherapy delivery. More prospective clinical studies are required to determine the optimal chemoradiation regimen in head and neck squamous cell carcinoma.
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Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/radioterapia , Centros de Atenção Terciária , Adulto , Idoso , Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiorradioterapia , Esquema de Medicação , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND AND PURPOSE: This study quantifies intrafraction motion in surface-guided radiotherapy (SGRT) for breast cancer and considers the need for individualized intrafraction motion measures when calculating Planning Target Volume (PTV) margins. METHODS: SGRT was used to assess intrafraction motion in consecutive patients according to (1) site irradiated (whole breast (WB)/chest wall (CW) versus WB/CWâ¯+â¯regional lymph nodes) and (2) the use of deep inspiration breath hold (DIBH) versus free-breathing (FB). Intrafraction motion variation was evaluated throughout the treatment course for all cases. Associations between intrafraction motion and patient specific characteristics were explored. The usefulness of individualised intrafraction motion measures for PTV margin determination was considered. RESULTS: 102 patients undergoing 1360 fractions were included. On a population level, average intrafraction motion was less than 0.4mm and 0.2 degrees for translational and rotational directions, respectively, with 95th percentiles < 1.2mm and 0.6 degrees. No clinically meaningful differences in intrafraction motion were observed according to site irradiated or the use of DIBH. Consistency in intrafraction motion was noted for all patients throughout the treatment course. No clinically meaningful associations were found between intrafraction motion and patient specific characteristics such as age, seroma volume, PTV volume, and mean body volume. CONCLUSION: Intrafractional deviations with SGRT, using manufacturer-recommended ROIs, are minimal, do not vary substantially for different treatment techniques or patient specific characteristics, and remain constant throughout the treatment course. A universal intrafraction motion measure may be sufficient for calculating PTV margins. Further validation studies are needed to evaluate the impact of ROI size and coverage.
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BACKGROUND: Osteoradionecrosis is a long-term, serious side effect of head and neck radiation therapy and is associated with significant morbidity and quality of life issues. METHODS: This paper sought to determine consensus on the prevention and management of osteoradionecrosis by an international panel of multidisciplinary professionals expert in the management of patients with head and neck cancer using a Delphi methodology. Unique to this work is our direct inclusion of the views of patients and carers in our findings. RESULTS: This study reached consensus on the importance of pre and post oral health assessment and education for patients with head and neck cancer. This was also noted by the patients and carers who took part in the study. CONCLUSIONS: This work highlights the need for a standardized oral health assessment tool and multidisciplinary care of patients to prevent and manage osteoradionecrosis.
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OBJECTIVES: Despite the unfavorable outcomes associated with continued smoking, a substantial proportion of patients with cancer continue to smoke after diagnosis. However, limited use of smoking cessation (SC) interventions has been reported. This study explored the perceptions of patients with cancer who continue to smoke/recently quit regarding SC. DATA SOURCES: Semistructured phone/Zoom/Webex interviews were conducted with 25 participants attending four Irish cancer hospitals who were current smokers or had quit at/after their cancer diagnosis. Thematic analysis was used to analyze the data. CONCLUSION: A total of four key themes emerged: (1) Diagnosis was a shock and a cue to action. (2) Brief and variable SC support: most participants did not feel stigmatized and reported receiving verbal or written information from oncology healthcare providers (HCPs) on SC supports. However, use of SC services was limited and largely ineffective. Some participants reported that SC discussions occurred earlier in their treatment with limited/no discussion later. (3) Facilitators vs barriers: the presence or absence of willpower and motivation was perceived as important. Family and HCP support helped while stress hindered SC. (4) SC support is a "marathon," not a "sprint." Patients with cancer who continue to smoke or recently quit want a sustained, tailored, nonjudgmental approach to SC incorporating pharmacological and behavioral interventions that span hospital-/community-based settings. IMPLICATIONS FOR NURSING PRACTICE: While consultants have been identified as the key HCP to initiate the SC discussion, oncology nurses can support patients with cancer who smoke/recently quit by advocating for comprehensive SC services and by using positive messaging and encouragement.
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Neoplasias , Abandono do Hábito de Fumar , Humanos , Masculino , Feminino , Abandono do Hábito de Fumar/psicologia , Abandono do Hábito de Fumar/métodos , Pessoa de Meia-Idade , Neoplasias/psicologia , Adulto , Idoso , Irlanda , Fumar/psicologia , Apoio SocialRESUMO
The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website.
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Ensaios Clínicos como Assunto , Consenso , Bases de Dados Factuais , Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/terapia , Bases de Dados Factuais/normas , Ensaios Clínicos como Assunto/normas , Técnica Delphi , Pesquisa Biomédica/normasRESUMO
Background Characterization of the sexual behaviours and lifestyle factors associated with human papillomavirus (HPV)-positive oral cavity and oropharyngeal squamous cell carcinoma (OPSCC) is crucial to optimal counselling. Our study aims to investigate the relationship between sexual behaviours, lifestyle factors and HPV-positive OPSCC in an Irish population. Methods We performed a case-control study of 60 patients with newly diagnosed HPV-positive and HPV-negative oral cavity and OPSCC. Results Oral sexual activity was more common in the HPV-positive tumour subgroup; however, this association was insignificant on multivariate analysis. No association between age of onset of sexual activity, number of sexual partners or practicing anal sex and HPV-positivity was found. The HPV-positive tumour subgroup had significantly less tobacco use than their HPV-negative counterparts (OR 0.93, 95% CI 0.90-0.97). Conclusion The emergence of HPV-positive OPSCC means head and neck surgeons must adopt new roles as counsellors of sexually transmitted disease, in addition to their previous role of delivering a cancer diagnosis.
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BACKGROUND: Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck. METHODS: This is a multicentre phase II study randomizing 90 patients with T1-4 N0-2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL. DISCUSSION: This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03997643 . Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.
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Quimioterapia Adjuvante/efeitos adversos , Transtornos de Deglutição/prevenção & controle , Esvaziamento Cervical/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Orofaríngeas/terapia , Radioterapia/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Orofaríngeas/patologia , Prognóstico , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida , Adulto JovemAssuntos
Serviços de Saúde Comunitária , Participação da Comunidade , Retroalimentação , Acessibilidade aos Serviços de Saúde , Comportamento de Ajuda , Transtornos Mentais/enfermagem , Transtornos Mentais/reabilitação , Medicina Estatal , Inglaterra , Grupos Focais , Humanos , Avaliação de Resultados em Cuidados de Saúde , Melhoria de QualidadeRESUMO
INTRODUCTION: Adjuvant radiotherapy is proven to prevent lymph node field relapse after therapeutic lymphadenectomy for melanoma, but does not improve overall survival based on current data. There remains a high rate of distant relapse. This study reports patterns of failure in patients treated with adjuvant radiotherapy, looking at factors associated with distant metastasis and comparing this to recent literature. METHODS: This retrospective study included patients treated with adjuvant nodal irradiation after lymphadenectomy between June 2012 and March 2015. RESULTS: Twenty-one patients were treated during this period. Median follow-up was 13.5 months. There were no lymph node field recurrences. Distant metastasis (DM) rate was 48%. DM rate was significantly higher (P = 0.027) in patients with extracapsular extension (ECE) (71%) than those without ECE (0%). DM rate was higher in those with a maximum tumour size of >3 cm (71%) than those with tumour size <3 cm (30%) (P = 0.160). Number of nodes, BRAF status or nodal site did not correlate with rate of DM. The median time to DM was 16 weeks after completion of radiotherapy. CONCLUSION: Radiotherapy is well tolerated and effective in regional control. However, patients are at risk of early distant relapse, particularly those with ECE or large tumour size. There are currently no useful prognostic markers to differentiate the risk of regional versus distant recurrence, and the optimal treatment paradigm remains undefined. Research on adjuvant systemic therapies and abscopal effects of radiotherapy have shown improved management of distant metastasis; creating an even greater need for effective regional control strategies.
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Melanoma/radioterapia , Radioterapia Adjuvante , Neoplasias Cutâneas/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Falha de Tratamento , Resultado do TratamentoRESUMO
Hypofractionated radiation therapy (RT) regimes in non-small cell lung cancer (NSCLC) have become increasingly popular with a number of international trials currently underway. The majority of the dose-volume-constraints (DVCs) published in the literature refer to conventional 2Gy per fraction deliveries. Here relevant organs-at-risk (OARs) are identified and available dose-volume constraint data discussed and summarised for moderately hypofractionated NSCLC regimes. The OARs examined include lung, brachial plexus, heart, oesophagus, airway and spinal cord. Where available the toxicity rates are also reported with all data summarised tabulated to aid its use in the clinic.
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Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Plexo Braquial/efeitos da radiação , Esôfago/efeitos da radiação , Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Órgãos em Risco , Dosagem RadioterapêuticaRESUMO
CONTEXT: Hypothalamic-pituitary (HP) dysfunction is common in children treated with cranial radiotherapy (RT) for brain tumors, but there is little known about the risk of HP dysfunction in adults treated with RT for primary nonpituitary brain tumors. OBJECTIVE: The objective was to study the frequency of HP dysfunction in adults after RT for nonpituitary brain tumors. METHOD: We studied 56 adult patients who received external beam RT for primary nonpituitary brain tumors at time intervals of 12-150 months after RT. The control group consisted of 20 RT-naive patients with primary brain tumors. GH and adrenal axes were assessed using the insulin tolerance test or the glucagon stimulation test. Gonadotroph, thyrotroph, and lactotroph function were assessed using baseline blood measurements. The biological effective dose (BED) to the HP axis was calculated in the RT patients. RESULTS: Hypopituitarism was present in 41% of patients. The frequency of GH, ACTH, gonadotropin, and TSH deficiencies, and hyperprolactinemia was 32, 21, 27, 9, and 32%, respectively. Any degree of hypopituitarism and GH deficiency was significantly associated with longer time interval from RT and greater BED. However, gonadotropin deficiency and hyperprolactinemia were only related to BED, whereas ACTH deficiency was only significantly associated with the time interval from RT. One RT-naive patient was GH deficient. CONCLUSION: Adult patients treated with cranial irradiation for primary nonpituitary brain tumors are at high risk of hypopituitarism, which is time and dose dependent. Long-term surveillance and periodic evaluation are needed. We recommend that adult late effect clinics, similar to those for children, should be established.
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Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Lesões por Radiação/fisiopatologia , Hormônio Adrenocorticotrópico/deficiência , Adulto , Estudos de Casos e Controles , Relação Dose-Resposta à Radiação , Feminino , Gonadotropinas/deficiência , Hormônio do Crescimento Humano/deficiência , Humanos , Hiperprolactinemia/etiologia , Hipopituitarismo/etiologia , Hipopituitarismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Aceleradores de Partículas , Lesões por Radiação/complicações , Fatores de Risco , Tireotropina/deficiência , Fatores de TempoRESUMO
We have sequenced two sections of chloroplast DNA from adzuki bean (Vigna angularis), containing the junctions between the inverted repeat (IR) and large single copy (LSC) regions of the genome. The gene order at both junctions is different from that described for other members of the legume family, such as Lotus japonicus and soybean. These differences have been attributed to an apparent 78-kb inversion that spans nearly the entire LSC region and which is present in adzuki and its close relative, the common bean. This 78-kb rearrangement broke the large S10 operon of ribosomal proteins into two smaller operons, one at each end of the LSC, without affecting the gene content of the genome. It disrupted the physical and transcriptional relationship between the six-gene rpl23-rpl14 cluster and the four-gene rps8-rpoA cluster that is conserved in most land plants. Analysis of the endpoints of the rearrangement indicates that it probably occurred by means of a two-step process of expansion and contraction of the IR and not by a 78-kb inversion.
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DNA de Cloroplastos , Evolução Molecular , Fabaceae/genética , Sequências Repetitivas de Ácido Nucleico , Sequência de Bases , Cloroplastos/genética , Modelos Genéticos , Dados de Sequência Molecular , PseudogenesRESUMO
INTRODUCTION: A recent meta-analysis suggested that patients with non-small-cell lung cancer (NSCLC) whose primary tumors have a higher standardized uptake value (SUV) derived from F-fluorodeoxyglucose positron emission tomography (PET) have a worse prognosis in comparison with those with tumors with lower values. However, previous analyses have had methodological weaknesses. Furthermore, the prognostic significance over the full range of SUV values in patients treated nonsurgically remains unclear. The aim of this retrospective study was to investigate the relationship between survival and maximum SUV (SUV(max)) analyzed as a continuous variable, in patients with NSCLC, staged using PET/computed tomography (CT) and treated with radiotherapy with or without chemotherapy. METHODS: Eligible patients had a histological diagnosis of NSCLC, were treated with radical radiotherapy with or without chemotherapy as their primary treatment, and had pretreatment PET/CT scans. SUV(max), defined as the maximum pixel SUV value retrieved from the primary tumor, was analyzed primarily as a continuous variable for overall survival. RESULTS: Eighty-eight patients met eligibility criteria: stage I, 19; stage II, 10; and stage III, 59. Median SUV(max) was 15.0 (range, 2.5-56). Higher stage was associated with higher SUV(max) values (p = 0.048). In univariate analysis, there was no evidence of a prognostic effect of SUV(max) (hazard ratio per doubling = 0.83; 95% confidence interval, 0.62-1.11; p = 0.22). Analyzing SUV(max) as a dichotomous variable (median cut point = 15.0), the hazard ratio (high: low) for risk of death was 0.71, with p = 0.18 (95% confidence interval, 0.44-1.15). CONCLUSIONS: In this cohort of patients, increasing SUV(max) derived from F-fluorodeoxyglucose-PET/CT was associated with increasing tumor, node, metastasis (TNM) stage. We found no evidence of an association of increasing SUV(max) with a shorter survival. Previous reports of an association between prognosis and SUV(max) may partly be the result of methodological differences between this study and previous reports and an association between stage and SUV(max).
Assuntos
Adenocarcinoma/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Fluordesoxiglucose F18 , Neoplasias Pulmonares/mortalidade , Compostos Radiofarmacêuticos , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Carga TumoralRESUMO
BACKGROUND: An unexpected finding from the phase III parotid sparing radiotherapy trial, PARSPORT (ISRCTN48243537, CRUK/03/005), was a statistically significant increase in acute fatigue for those patients who were treated with intensity-modulated radiotherapy (IMRT) compared to standard conventional radiotherapy (CRT). One possible explanation was the difference in dose to central nervous system (CNS) structures due to differing beam portals. Using data from the trial, a dosimetric analysis of individual CNS structures was performed. METHOD: Dosimetric and toxicity data were available for 67 patients (27 CRT, 40 IMRT). Retrospective delineation of the posterior fossa, brainstem, cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia was performed. Dosimetry was reviewed using summary statistics and dose-volume atlases. RESULTS: A statistically significant increase in maximum and mean doses to each structure was observed for patients who received IMRT compared to those who received CRT. Both maximum and mean doses were significantly higher for the posterior fossa, brainstem and cerebellum for the 42 patients who reported acute fatigue of Grade 2 or higher (p ≤ 0.01) compared to the 25 who did not. Dose-volume atlases of the same structures indicated that regions representing larger volumes and higher doses to each structure were consistent with a higher incidence of acute fatigue. There was no association between the dose distribution and acute fatigue for the other structures tested. CONCLUSIONS: The excess fatigue reported in the IMRT arm of the trial may, at least in part, be attributed to the dose distribution to the posterior fossa, cerebellum and brainstem. Future studies that modify dose delivery to these structures may allow us to test the hypothesis that radiation-induced fatigue is avoidable.
Assuntos
Fadiga/etiologia , Neoplasias Parotídeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Idoso , Sistema Nervoso Central/efeitos da radiação , Relação Dose-Resposta à Radiação , Fadiga/epidemiologia , Fadiga/fisiopatologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Radiometria/métodos , Radioterapia/efeitos adversos , Radioterapia/métodos , Dosagem Radioterapêutica , Medição de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
The radiotherapy conformity index (CI) is a useful tool to quantitatively assess the quality of radiotherapy treatment plans, and represents the relationship between isodose distributions and target volume. A conformity index of unity implies high planning target volume (PTV) coverage and minimal unnecessary irradiation of surrounding tissues. We performed this analysis to describe the CI for lung cancer 3-dimensional conformal radiotherapy (3DCRT) and to identify clinical and technical determinants of CI, as it is not known which factors are associated with good quality 3D conformal radiotherapy treatment planning. Radiotherapy treatment plans from a database of 52 patients with inoperable Stage 1 to 3b lung cancer, on a hypofractionated 3DCRT trial were evaluated. A CI was calculated for all plans using the definition of the ICRU 62:CI = (TV/PTV), which is the quotient of the treated volume (TV) and the PTV. Data on patient, tumor, and planning variables, which could influence CI, were recorded and analyzed. Mean CI was 2.01 (range = 1.06-3.8). On univariate analysis, PTV (p = 0.023), number of beams (p = 0.036), medial vs. lateral tumor location (p = 0.016), and increasing tumor stage (p = 0.041) were associated with improved conformity. On multiple regression analysis, factors found to be associated with CI included central vs. peripheral tumor location (p = 0.041) and PTV size (p = 0.058). The term 3DCRT is used routinely in the literature, without any indication of the degree of conformality. We recommend routine reporting of conformity indices. Conformity indices may be affected by both planning variables and tumor factors.