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BACKGROUND: Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved to treat locally advanced/metastatic urothelial carcinoma (mUC) in patients with susceptible FGFR3/2 alterations (FGFRalt) who progressed after platinum-containing chemotherapy. FGFR-altered tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti-programmed death-(ligand) 1 [PD-(L)1] treatment. This cohort in the randomized, open-label phase III THOR study assessed erdafitinib versus pembrolizumab in anti-PD-(L)1-naive patients with mUC. PATIENTS AND METHODS: Patients ≥18 years with unresectable advanced/mUC, with select FGFRalt, disease progression on one prior treatment, and who were anti-PD-(L)1-naive were randomized 1 : 1 to receive erdafitinib 8 mg once daily with pharmacodynamically guided uptitration to 9 mg or pembrolizumab 200 mg every 3 weeks. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: The intent-to-treat population (median follow-up 33 months) comprised 175 and 176 patients in the erdafitinib and pembrolizumab arms, respectively. There was no statistically significant difference in OS between erdafitinib and pembrolizumab [median 10.9 versus 11.1 months, respectively; hazard ratio (HR) 1.18; 95% confidence interval (CI) 0.92-1.51; P = 0.18]. Median PFS for erdafitinib and pembrolizumab was 4.4 and 2.7 months, respectively (HR 0.88; 95% CI 0.70-1.10). ORR was 40.0% and 21.6% (relative risk 1.85; 95% CI 1.32-2.59) and median duration of response was 4.3 and 14.4 months for erdafitinib and pembrolizumab, respectively. 64.7% and 50.9% of patients in the erdafitinib and pembrolizumab arms had ≥1 grade 3-4 adverse events (AEs); 5 (2.9%) and 12 (6.9%) patients, respectively, had AEs that led to death. CONCLUSIONS: Erdafitinib and pembrolizumab had similar median OS in this anti-PD-(L)1-naive, FGFR-altered mUC population. Outcomes with pembrolizumab were better than assumed and aligned with previous reports in non- FGFR-altered populations. Safety results were consistent with the known profiles for erdafitinib and pembrolizumab in this patient population.
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Carcinoma de Células de Transição , Pirazóis , Quinoxalinas , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Extended field radiotherapy is a standard of care for low volume stage II testicular seminoma. We hypothesized that neoadjuvant carboplatin might reduce the recurrence risk. PATIENTS AND METHODS: In a single-arm study, 51 patients were treated between May 1996 and November 2011 with a single cycle of carboplatin followed by radiotherapy. The radiation field was reduced from an extended abdomino-pelvic field to just the para-aortic region, and the radiation dose from 35 Gy to 30 Gy in 39 patients. RESULTS: After a median follow-up of 55 months (range 8-151 months) with 38 (74%) of the patients having been followed for >2 years, there have been no relapses (95% confidence limits of 5-year relapse-free survival of 93%-100%). Toxicity has been low with grade 3 toxicity limited to four patients with grade 3 haematological toxicity (with no clinical sequelae) and one patient with grade 3 nausea (during radiotherapy). No patients experienced grade 4 toxicity. CONCLUSIONS: The results of this pilot study suggest that a single cycle of neoadjuvant carboplatin before radiotherapy may reduce recurrence risk compared with radiotherapy alone and permit a smaller radiation field, and this approach is proposed for further investigation.
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Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Seminoma/tratamento farmacológico , Seminoma/radioterapia , Adolescente , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/radioterapia , Adulto JovemRESUMO
In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, â¼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
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Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Europa (Continente) , Seguimentos , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/classificação , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Taxa de SobrevidaRESUMO
Testicular germ-cell tumours (TGCT) are the most frequent solid tumour to affect young Caucasian adult males and have increased in incidence over recent decades. In clinical stage I non-seminomas, (NSGCT) histological vascular invasion (VI) is a prognostic factor for metastatic relapse. Using array comparative genomic hybridization, we have previously shown that the presence of VI is associated with gain of a region at 17q12, containing a cluster of genes encoding inflammatory cytokines. We here confirm this finding using fluorescence in situ hybridization (FISH) demonstrating gain in 12 out of 42 (29%) assessable samples. Interrogation of previously published expression microarray data suggests that of the genes contained within this region, CCL2 [monocyte chemoattractant protein 1 (MCP1)] is frequently overexpressed in TGCT. Immunohistochemistry confirms this finding in a collection of 67 clinical stage I NSGCT, demonstrating an association with the presence of VI (p=0.049) that was not seen with VEGF-A, MMP2 or MMP9, although all were frequently expressed. This work gives further insight into the mechanisms involved in invasion in this tumour type, which may ultimately have implications for the management of patients with stage I disease.
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Biomarcadores Tumorais/biossíntese , Quimiocina CCL2/biossíntese , Genoma Humano , Neoplasias Embrionárias de Células Germinativas/irrigação sanguínea , Neoplasias Testiculares/irrigação sanguínea , Adolescente , Adulto , Cromossomos Humanos Par 17/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Neovascularização Patológica , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
INTRODUCTION: Online MRI guided adaptive radiotherapy (MRIgRT) is resource intensive. To maintain and increase uptake traditional roles and responsibilities may need refining. This novel study aims to provide an in-depth understanding and subsequent impact of the roles required to deliver on-line adaptive MRIgRT by exploring the current skills and knowledge of radiographers. METHOD: A purposive sampling approach was used to invite radiographers, clinicians and physicists from centres with experience of MRIgRT to participate. Focus Group Interviews were conducted with two facilitators using a semi-structure interview guide (Appendix 1). Four researchers independently familiarised themselves and coded the data using framework analysis. A consensus thematic framework of ptive Radiotherapy codes and categories was agreed and systematically applied. RESULTS: Thirty participants took part (Radiographers: N = 18, Physicists: N = 9 and Clinicians: N = 3). Three key themes were identified: 'Current MRIgRT', 'Training' and 'Future Practice'. Current MRIgRT identified a variation in radiographers' roles and responsibilities with pathways ranging from radiographer-led, clinician-light-led and MDT-led. The consensus was to move towards radiographer-led with the need to have a robust on-call service heavily emphasised. Training highlighted the breadth of knowledge required by radiographers including MRI, contouring, planning and dosimetry, and treatment experience. Debate was presented over timing and length of training required. Future Practice identified the need to have radiographers solely deliver MRIgRT, to reduce staff present which was seen as a main driver, and time and resources to train radiographers seen as the main barriers. CONCLUSION: Radiographer-led MRIgRT is an exciting development because of the potential radiographer role development. A national training framework created collaboratively with all stakeholders and professions involved would ensure consistency in skills and knowledge. IMPLICATIONS FOR PRACTICE: Role development and changes in education for therapeutic radiographers.
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Pessoal Técnico de Saúde , Radioterapia Guiada por Imagem , Grupos Focais , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Interaction between the chemokine CXCL12 (SDF1) and the G-protein coupled receptor CXCR4 is responsible for the maintenance of adult stem cell niches and is known to play an important role in utero in the migration of primordial germ cells. We demonstrate expression of CXCL12 by Sertoli cells and confirm CXCR4 expression by the germ cell population of the adult human testes. CXCR4 is also known to mediate organ-specific patterns of metastases in a range of common cancers. We identify consistent expression of CXCR4 mRNA and protein in testicular germ cell tumours (TGCT) that accounts for their patterns of relapse in sites of known CXCL12 expression. Extragonadal primary germ cell tumours express CXCR4 and their sites of occurrence are coincident with areas of known CXCL12 expression in utero. We show that CXCL12 stimulates the invasive migration of a TGCT cell line in vitro in a CXCR4-dependent fashion and activates ERK. Furthermore, we demonstrate that expression of CXCL12 in stage I non-seminomas is significantly associated with organ-confined disease post-orchidectomy and reduced risk of relapse (p = 0.003). This may be through the loss of CXCL12 gradients that might otherwise attract cells away from the primary tumour. We propose CXCL12 expression as a potential predictor of subsequent relapse that could lead to avoiding unnecessary treatment and associated late toxicities. Our observations support a role for CXCL12/CXCR4 in the adult germ cell population and demonstrate pathological function in germ cell tumour development and metastasis that may have clinical utility.
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Biomarcadores Tumorais/metabolismo , Quimiocina CXCL12/metabolismo , Neoplasias Embrionárias de Células Germinativas/metabolismo , Receptores CXCR4/metabolismo , Neoplasias Testiculares/metabolismo , Testículo/metabolismo , Adolescente , Adulto , Idoso , Quimiotaxia , Intervalo Livre de Doença , Ativação Enzimática , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Neoplasias Testiculares/patologia , Células Tumorais Cultivadas , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: The uptake of new technologies has varied internationally and there have often been barriers to implementation. On-line adaptive radiotherapy (ART) promises to improve patient outcome. This survey focuses on the implementation phase of delivering ART and professional roles and responsibilities currently involved in the workflow and changes which may be expected in the future. MATERIALS AND METHODS: A 38 question survey included aspects on current practice; professional responsibilities; benefits and barriers; and decision making and responsibilities. For the purposes of the questionnaire and paper, ART was considered where tumour and /or organs at risk were contoured and re-planning was performed on-line. The questionnaire was electronically distributed via radiotherapy networks. RESULTS: Nineteen international responses were received. Europe (nâ¯=â¯11), United States of America (nâ¯=â¯4); Canada (nâ¯=â¯2), Australia (nâ¯=â¯1) and Hong Kong (nâ¯=â¯1). The majority of centres started using ART in either 2018 (nâ¯=â¯7) or 2019 (nâ¯=â¯6). Four centres started treating with ART between 2015 and 2017, and the first was in 2014. Centres initially treated prostate and oligometastases patients, expanding to treat prostate, oligometastases, pancreas and rectum. The majority of centres were working in conventional roles, however moving towards radiographers taking more responsibility in contouring organs at risk (OAR), target and dosimetry. The three most important criteria chosen by medical doctors to determine if ART should be used were overall gross anatomy changes of target and OAR, target not covered by planning target volume (PTV) and OAR close to the high dose area. There was no clear consensus on the minimum improvement in dose to target or reduction in dose to OAR to warrant adaption. CONCLUSION: On-line ART has been implemented successfully internationally. Initial practice maintains conventional professional roles and responsibilities, however there is trend to changing roles for the future. There is little consensus regarding the triggers of adaption.
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AIMS: Node-positive bladder cancer (NPBC) carries a poor prognosis and has traditionally been treated palliatively. However, surgical series suggest that a subset of NPBC patients can achieve long-term control after cystectomy and lymph node dissection. There is little published data regarding the use of radiotherapy to treat NPBC patients. This is in part due to concerns regarding the toxicity of whole-pelvis radiotherapy using conventional techniques. We hypothesised that, using intensity-modulated radiotherapy (IMRT), the pelvic nodes and bladder could be treated within a radical treatment volume with acceptable toxicity profiles. MATERIALS AND METHODS: The Intensity-modulated Pelvic Node and Bladder Radiotherapy (IMPART) trial was a phase II single-centre prospective study designed to assess the feasibility of delivering IMRT to treat the bladder and pelvic nodes in patients with node-positive or high-risk node-negative bladder cancer (NNBC). The primary end point was meeting predetermined dose constraints. Secondary end points included acute and late toxicity, pelvic relapse-free survival and overall survival. RESULTS: In total, 38 patients were recruited and treated between June 2009 and November 2012; 22/38 (58%) had NPBC; 31/38 (81.6%) received neoadjuvant chemotherapy; 18/38 (47%) received concurrent chemotherapy; 37/38 (97%) patients had radiotherapy planned as per protocol. Grade 3 gastrointestinal and genitourinary acute toxicity rates were 5.4 and 20.6%, respectively. At 1 year, the grade 3 late toxicity rate was 5%; 1-, 2- and 5-year pelvic relapse-free survival rates were 55, 37 and 26%, respectively. The median overall survival was 1.9 years (95% confidence interval 1.1-3.8) with 1-, 2- and 5-year overall survival rates of 68, 50 and 34%, respectively. CONCLUSION: Delivering IMRT to the bladder and pelvic nodes in NPBC and high-risk NNBC is feasible, with low toxicity and low pelvic nodal recurrence rates. Long-term control seems to be achievable in a subset of patients. However, relapse patterns suggest that strategies targeting both local recurrence and the development of distant metastases are required to improve patient outcomes.
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Linfonodos/efeitos da radiação , Pelve/efeitos da radiação , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Pelve/patologia , Estudos ProspectivosRESUMO
AIMS: To assess the activity of a continuous infusion of 5-fluorouracil in patients with recurrent locally advanced or metastatic transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: Eight centres within the UK entered 50 patients into the study. Twenty-four weeks of continuously infused 5-fluorouracil, 300mg/m(2)/day through a mini-pump, were planned. The primary outcome was tumour response at 8 weeks after the start of treatment. RESULTS: The median age of the patients was 68 years and 37 (80.4%) had a World Health Organization performance status of 0 or 1. The overall response rate at 8 weeks, according to the response evaluation criteria in solid tumors (RECIST) criteria in 46 evaluable patients, was 15% (95% confidence interval 5-26%) and 20% (95% confidence interval 8-31%) when assessments at all time points were included. The median progression-free survival was 1.9 months (95% confidence interval 1.8-2.7 months) and the median overall survival was 6.5 months (95% confidence interval 4.1-8.5 months). The most frequent grade 3/4 toxicities were mucositis and diarrhoea (each in 6.5% of patients) and nausea/vomiting and hand-foot syndrome (each in 4.3% of patients). CONCLUSIONS: Continuous infusional 5-fluorouracil has activity in transitional cell carcinoma of the urinary tract. Prolonged fluoropyrimidine administration may be a useful component of future combination regimens for this disease, particularly in patients with poor renal function.
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Antineoplásicos/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Fluoruracila/administração & dosagem , Bombas de Infusão , Neoplasias Urológicas/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Feminino , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Análise de SobrevidaRESUMO
AIMS: Magnetic resonance imaging (MRI) is an effective method for evaluating the spine in patients with a high risk of metastatic disease. The aim of this study was to compare MRI spine with radionuclide bone scan in detecting spinal metastases for staging prostate cancer patients. MATERIALS AND METHODS: A cohort of 99 patients with locally advanced prostate cancer at high risk of skeletal metastasis (prostate-specific antigen>10 ng/ml, composite Gleason score>or=8) or equivocal findings on bone scan were included in the retrospective study, and their MRI spine and bone scans were analysed. RESULTS: Ten patients were detected to have definite spinal metastasis by bone scan, whereas 12 patients had definite skeletal metastasis by MRI spine. Compared with the 'gold standard', derived from clinical and radiological follow-up, the sensitivities for radionuclide bone scan and that for MRI spine for detecting skeletal metastasis were 71.4 and 85.7%, respectively (P=0.023), whereas the specificities were 96.5 and 97.7%, respectively (P=0.95). Of the 34 individual metastatic lesions in the spine, 15 were concordantly positive on both scans, whereas five lesions were positive only by bone scan and 11 positive only by MRI. The addition of MRI spine in the staging for prostate cancer resulted in a change of stage and management plan in seven (7%) patients. CONCLUSION: MRI spine has comparable specificity and slightly better sensitivity than bone scan to detect spinal metastasis from prostate cancer.
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Imageamento por Ressonância Magnética , Neoplasias da Próstata/patologia , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/secundário , Coluna Vertebral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Sensibilidade e Especificidade , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagemRESUMO
OBJECTIVES: To systematically identify the preferred magnetic resonance imaging (MRI) sequences following volunteer imaging on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac) for future protocol development. METHODS: Non-patient volunteers were recruited to a Research and Ethics committee approved prospective MR-only imaging study on a 1.5T MR Linac system. Volunteers attended 1-3 imaging sessions that included a combination of mDixon, T1w, T2w sequences using 2-dimensional (2D) and 3-dimensional (3D) acquisitions. Each sequence was acquired over 2-7 minutes and reviewed by a panel of 3 observers to evaluate image quality using a visual grading analysis based on a 4-point Likert scale. Sequences were acquired and modified iteratively until deemed fit for purpose (online image matching or re-planning) and all observers agreed they were suitable in 3 volunteers. RESULTS: 26 volunteers underwent 31 imaging sessions of six general anatomical regions. Images were acquired in one or two of six general anatomical regions: male pelvis (nâ¯=â¯9), female pelvis (nâ¯=â¯4), chestwall/breast (nâ¯=â¯5), lung/oesophagus (nâ¯=â¯5), abdomen (nâ¯=â¯3) and head and neck (nâ¯=â¯5). Images were acquired using a pre-defined exam-card that on average, included six sequences (range 2-10), with a maximum scan time of approximately one hour. The majority of observers preferred T2-weighted sequences. The thorax teams were the only groups to prefer T1-weighted imaging. CONCLUSIONS: An iterative process identified sequence agreement in all anatomical regions. These sequences will now be evaluated in patient volunteers. ADVANCES IN KNOWLEDGE: This manuscript is the first publication sharing the results of the first systematic selection of MRI sequences for use in on-board MRI-guided radiotherapy by end-users (therapeutic radiographers and clinical oncologists) in healthy volunteers.
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BACKGROUND: Testicular germ cell tumour (TGCT) is highly heritable but > 50% of the genetic risk remains unexplained. Epidemiological observation of greater relative risk to brothers of men with TGCT compared to sons has long alluded to recessively acting TGCT genetic susceptibility factors, but to date none have been reported. Runs of homozygosity (RoH) are a signature indicating underlying recessively acting alleles and have been associated with increased risk of other cancer types. OBJECTIVE: To examine whether RoH are associated with TGCT risk. METHODS: We performed a genome-wide RoH analysis using GWAS data from 3206 TGCT cases and 7422 controls uniformly genotyped using the OncoArray platform. RESULTS: Global measures of homozygosity were not significantly different between cases and controls, and the frequency of individual consensus RoH was not significantly different between cases and controls, after correction for multiple testing. RoH at three regions, 11p13-11p14.3, 5q14.1-5q22.3 and 13q14.11-13q.14.13, were, however, nominally statistically significant at p < 0.01. Intriguingly, RoH200 at 11p13-11p14.3 encompasses Wilms tumour 1 (WT1), a recognized cancer susceptibility gene with roles in sex determination and developmental transcriptional regulation, processes repeatedly implicated in TGCT aetiology. DISCUSSION AND CONCLUSION: Overall, our data do not support a major role in the risk of TGCT for recessively acting alleles acting through homozygosity, as measured by RoH in outbred populations of cases and controls.
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Homozigoto , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Genoma , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Testicular germ cell tumours (TGCTs) are the most common cause of cancer in men between the ages of 15 and 40 years, and, overall, the majority of patients should expect to be cured. The European Germ Cell Cancer Consensus Group has provided clear guidelines for the primary treatment of both seminoma and nonseminomatous germ cell tumours. There is, however, no international consensus on how best to follow patients after their initial management. This must promptly and reliably identify relapses without causing further harm. The standardising of follow-up would result in optimising risk-benefit ratios for individual patients, while ensuring economic use of resources. We have identified the seven common scenarios in managing seminomas and nonseminomas of the various stages and discuss the pertinent issues around relapse and follow-up. We review the available literature and present our comprehensive TGCT follow-up guidelines. Our protocols provide a pragmatic, easily accessible user-friendly basis for other centres to use or to adapt to suit their needs. Furthermore, this should enable future trials to address specific issues around follow-up giving meaningful and useful results.
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Medicina Baseada em Evidências , Neoplasias Testiculares/terapia , Adolescente , Adulto , Terapia Combinada , Seguimentos , Humanos , Masculino , Guias de Prática Clínica como Assunto , Recidiva , Neoplasias Testiculares/fisiopatologia , Neoplasias Testiculares/psicologiaRESUMO
AIMS: To quantify the inter-fractional variation in bladder volume and position during a course of bladder radiotherapy, and to assess the feasibility of reducing the planning target volume (PTV) internal margin using an empty bladder protocol. MATERIALS AND METHODS: Weekly computed tomography scans were taken immediately after micturition on 15 patients undergoing radical radiotherapy for bladder cancer. Bladder volume and positional variation were compared by co-registration of the serial computed tomography scans with the initial planning scan and a single 'full' scan at the onset of treatment for each patient. A PTV was generated on the initial planning scan using both our departmental standard of 1.5cm and a reduced 1cm isotropic internal margin around the target (whole bladder) and the relative proportion of the bladder breaching the PTV using both margins compared. RESULTS: The mean post void residual volume from the planning scan was 112cm(3) (standard deviation 42cm(3)). The mean weekly variation in bladder volume relative to the planning volume was 0-12% (standard deviation 20-34%) with no observable trends over time. No statistically significant differences were seen in the proportion of bladder breaching the 1.5 and 1cm internal margin (P=0.18). Regression analysis showed that it is possible to ensure complete coverage of the bladder with a 1cm margin, providing the volume did not exceed over 50% of the initial planning scan volume. CONCLUSION: Using an empty bladder protocol and where on-line imaging is available it is feasible to reduce the internal margin of the PTV from 1.5 to 1cm, providing the volumes do not exceed >50% of the planning scan volume.
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Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias da Bexiga Urinária/radioterapia , Fracionamento da Dose de Radiação , Humanos , Movimento (Física) , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/diagnóstico por imagemRESUMO
This prospective randomised controlled study of 40 patients could not show a statistically significant advantage with 6 months of pentoxifylline compared with standard measures for late radiation-induced rectal bleeding. However, a modest benefit cannot be excluded and larger randomised placebo-controlled trials with longer durations of pentoxifylline treatment may be justified.
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Pentoxifilina/uso terapêutico , Proctite/tratamento farmacológico , Lesões por Radiação/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Proctite/etiologiaRESUMO
AIMS: With a life expectancy similar to the general population, greater numbers of patients with Down's syndrome are being diagnosed with testicular cancer. Learning difficulties and medical co-morbidity are common in this patient population and may lead to non-standard oncological treatment. We aimed to identify and discuss management challenges in the treatment of these patients with chemotherapy and radiotherapy and report their clinical outcome. MATERIALS AND METHODS: The Royal Marsden Hospital urology database was searched from 1982 to 2005 to identify all cases of patients with Down's syndrome and histologically confirmed testicular cancer who were referred for consideration of chemotherapy or radiotherapy. RESULTS: Nine patients were identified, of whom eight received chemotherapy or radiotherapy. Two patients had bilateral tumours and four had crypto-orchidism. At the time of diagnosis, the patients were 21-50 years of age. Of the 11 tumours identified, nine were seminomas and two were malignant teratoma undifferentiated. Five patients presented with stage I disease, of whom three received carboplatin and one received para-aortic radiotherapy as adjuvant treatment. Three patients presented with stage II disease, of whom two were treated with carboplatin and one received combination chemotherapy followed by radiotherapy. One patient with stage IV disease was treated with carboplatin. Five of nine patients relapsed within 30 months, of whom three were successfully salvaged with radiotherapy and one with combination chemotherapy. CONCLUSION: After standard and non-standard therapy for seminoma, the relapse rate for patients in our cohort was high. Since relapsed disease is much more difficult to manage with combination chemotherapy on account of respiratory, cardiac and renal co-morbidity, adequate initial treatment is advised. Consideration of psycho-social issues and the multiple treatment strategies available is vital in delivering optimal care to patients with Down's syndrome and testicular cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Síndrome de Down/terapia , Neoplasias Testiculares/terapia , Adulto , Comorbidade , Criptorquidismo , Síndrome de Down/complicações , Síndrome de Down/tratamento farmacológico , Síndrome de Down/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Seminoma/complicações , Seminoma/diagnóstico , Seminoma/terapia , Teratoma/complicações , Teratoma/diagnóstico , Teratoma/terapia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/radioterapiaRESUMO
AIMS: Spinal cord compression (SCC) is the most significant complication due to skeletal metastasis from prostate cancer. The early detection of SCC is essential as the neurological status before treatment is the major determinant influencing outcome. The aim of this investigation was to determine the role of magnetic resonance imaging of the spine in detecting SCC or occult SCC in patients with metastatic prostate cancer with no functional neurological deficit (FND). MATERIALS AND METHODS: A retrospective analysis of the clinical data of 150 consecutive patients with metastatic prostate cancer and no FND, who had MRI of the spine from January 2001 to May 2005, was carried out. 'Overt SCC' on MRI was defined as the involvement or compression of either the spinal cord or the cauda equina by an epidural or intramedullary mass lesion and 'occult SCC' as metastatic disease causing impingement, indentation or loss of definition of the thecal sac, which were considered together for statistical purposes as radiological spinal cord compromise (rSCC). RESULTS: Twenty-four (16%) patients had overt SCC, whereas 17 (11.3%) patients had occult SCC. Seven patients had rSCC at multiple non-contiguous sites. The significant clinical determinants of rSCC on univariate analysis were extensive bone metastasis (P=0.005) and back pain (P=0.002). On multivariate analysis, both back pain (P=0.012) and extensive bone metastasis (P=0.047) significantly predicted for rSCC. CONCLUSION: A significant proportion (27.3%) of patients with metastatic prostate cancer may harbour overt or occult SCC in the absence of FND. MRI of the spine for the early diagnosis of SCC may be considered useful in patients with extensive skeletal metastasis and back pain.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Próstata/patologia , Compressão da Medula Espinal/diagnóstico , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/secundário , Idoso , Idoso de 80 Anos ou mais , Dor nas Costas/etiologia , Cauda Equina , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Compressão da Medula Espinal/etiologiaRESUMO
Observational studies have suggested anthropometric traits, particularly increased height are associated with an elevated risk of testicular cancer (testicular germ cell tumour). However, there is an inconsistency between study findings, suggesting the possibility of the influence of confounding factors. To examine the association between anthropometric traits and testicular germ cell tumour using an unbiased approach, we performed a Mendelian randomisation study. We used genotype data from genome wide association studies of testicular germ cell tumour totalling 5518 cases and 19,055 controls. Externally weighted polygenic risk scores were created and used to evaluate associations with testicular germ cell tumour risk per one standard deviation (s.d) increase in genetically-defined adult height, adult BMI, adult waist hip ratio adjusted for BMI (WHRadjBMI), adult hip circumference adjusted for BMI (HIPadjBMI), adult waist circumference adjusted for BMI (WCadjBMI), birth weight (BW) and childhood obesity. Mendelian randomisation analysis did not demonstrate an association between any anthropometric trait and testicular germ cell tumour risk. In particular, despite good power, there was no global evidence for association between height and testicular germ cell tumour. However, three SNPs for adult height individually showed association with testicular germ cell tumour (rs4624820: OR = 1.47, 95% CI: 1.41-1.55, p = 2.7 × 10-57 ; rs12228415: OR = 1.17, 95% CI: 1.11-1.22, p = 3.1 × 10-10 ; rs7568069: OR = 1.13, 95% CI: 1.07-1.18, p = 1.1 × 10-6 ). This Mendelian randomisation analysis, based on the largest testicular germ cell tumour genome wide association dataset to date, does not support a causal etiological association between anthropometric traits and testicular germ cell tumour aetiology. Our findings are more compatible with confounding by shared environmental factors, possibly related to prenatal growth with exposure to these risk factors occurring in utero.
Assuntos
Estatura , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Adulto , Estatura/genética , Índice de Massa Corporal , Genótipo , Humanos , Masculino , Modelos Estatísticos , Neoplasias Embrionárias de Células Germinativas/genética , Polimorfismo de Nucleotídeo Único , Distribuição Aleatória , Fatores de Risco , Neoplasias Testiculares/genética , Relação Cintura-QuadrilRESUMO
AIMS: To describe the distribution of enlarged lymph nodes by nodal group found radiologically in patients presenting with adenocarcinoma of the prostate. This will help to define which nodal groups should be treated during the pelvic radiotherapy of patients with less advanced disease. MATERIALS AND METHODS: The scans of 55 men presenting with prostate cancer and metastases to lymph nodes only were reviewed. Lymph nodes of 8 mm or more in size were considered to be enlarged. RESULTS: The medial external iliac (obturator) nodes were most commonly enlarged (75% of patients) followed by nodes in the para-aortic region (26%) and anterior internal iliac region (24%). Para-aortic lymph-node enlargement was uncommon in the absence of pelvic lymphadenopathy. Midline pre-sacral lymph-node enlargement was not observed. Incidence of enlarged lymph nodes in the lateral external iliac group was 18%, an area which may not be routinely included during radiotherapy. CONCLUSION: There is a case for studying further the role of including lateral external iliac lymph nodes in the pelvic radiotherapy volume, as there may be an appreciable risk of lymph-node spread to this area.