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1.
JCO Clin Cancer Inform ; 8: e2400025, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38924710

RESUMO

PURPOSE: Real-world data (RWD) collected on patients treated as part of routine clinical care form the basis of cancer clinical registries. Capturing accurate death data can be challenging, with inaccurate survival data potentially compromising the integrity of registry-based research. Here, we explore the utility of data linkage (DL) to state-based registries to enhance the capture of survival outcomes. METHODS: We identified consecutive adult patients with brain tumors treated in the state of Victoria from the Brain Tumour Registry Australia: Innovation and Translation (BRAIN) database, who had no recorded date of death and no follow-up within the last 6 months. Full name and date of birth were used to match patients in the BRAIN registry with those in the Victorian Births, Deaths and Marriages (BDM) registry. Overall survival (OS) outcomes were compared pre- and post-DL. RESULTS: Of the 7,346 clinical registry patients, 5,462 (74%) had no date of death and no follow-up recorded within the last 6 months. Of the 5,462 patients, 1,588 (29%) were matched with a date of death in BDM. Factors associated with an increased number of matches were poor prognosis tumors, older age, and social disadvantage. OS was significantly overestimated pre-DL compared with post-DL for the entire cohort (pre- v post-DL: hazard ratio, 1.43; P < .001; median, 29.9 months v 16.7 months) and for most individual tumor types. This finding was present independent of the tumor prognosis. CONCLUSION: As revealed by linkage with BDM, a high proportion of patients in a brain cancer clinical registry had missing death data, contributed to by informative censoring, inflating OS calculations. DL to pertinent registries on an ongoing basis should be considered to ensure accurate reporting of survival data and interpretation of RWD outcomes.


Assuntos
Confiabilidade dos Dados , Sistema de Registros , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Registro Médico Coordenado/métodos , Idoso de 80 Anos ou mais , Prognóstico , Armazenamento e Recuperação da Informação
2.
J Neurooncol ; 168(2): 299-306, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38630385

RESUMO

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/mortalidade , Idoso , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Temozolomida/uso terapêutico , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Fatores Etários , Terapia Combinada , Resultado do Tratamento , Gerenciamento Clínico
3.
J Neurooncol ; 166(3): 395-405, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38321326

RESUMO

PURPOSE: Brain tumours are associated with neurocognitive impairments that are important for safe driving. Driving is vital to maintaining patient autonomy, despite this there is limited research on driving capacity amongst patients with brain tumours. The purpose of this review is to examine MVC risk in patients with brain tumours to inform development of clearer driving guidelines. METHODS: A systematic review was performed using Medline and EMBASE. Observational studies were included. The outcome of interest was MVC or measured risk of MVC in patients with benign or malignant brain tumours. Descriptive analysis and synthesis without meta-analysis were used to summarise findings. A narrative review of driving guidelines from Australia, United Kingdom and Canada was completed. RESULTS: Three studies were included in this review. One cohort study, one cross-sectional study and one case-control study were included (19,135 participants) across United States and Finland. One study evaluated the incidence of MVC in brain tumour patients, revealing no difference in MVC rates. Two studies measured MVC risk using driving simulation and cognitive testing. Patients found at higher risk of MVC had greater degrees of memory and visual attention impairments. However, predictive patient and tumour characteristics of MVC risk were heterogeneous across studies. Overall, driving guidelines had clear recommendations on selected conditions like seizures but were vague surrounding neurocognitive deficits. CONCLUSION: Limited data exists regarding driving behaviour and MVC incidence in brain tumour patients. Existing guidelines inadequately address neurocognitive complexities in this group. Future studies evaluating real-world data is required to inform development of more applicable driving guidelines. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2023 CRD42023434608.


Assuntos
Acidentes de Trânsito , Neoplasias Encefálicas , Humanos , Estados Unidos , Acidentes de Trânsito/psicologia , Estudos de Coortes , Estudos de Casos e Controles , Estudos Transversais , Veículos Automotores , Neoplasias Encefálicas/epidemiologia
4.
Trials ; 24(1): 92, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36747274

RESUMO

BACKGROUND: Randomised controlled trials (RCTs) are considered the "gold standard" for evaluating the effectiveness of interventions in clinical research. However, conventional RCTs are typically complex, expensive, and have narrow eligibility criteria, which limits generalisability. Registry-based randomised controlled trials (RRCTs) are an alternative approach that integrates the internal validity of an RCT with the external validity of a clinical registry by recruiting real-world patients and leveraging an existing registry platform for data collection. As RRCT is a novel research design, there has been limited research on the feasibility and acceptability of RRCTs from the patients' and trial team's perspectives. This study aims to explore patients', clinicians', and study coordinators' perspectives towards participation in and conduct of oncology RRCTs in Australia. METHODS: Thirty-seven semi-structured interviews were conducted with 15 cancer patients, 15 clinicians, and 7 study coordinators. Interviews were audio-recorded and transcribed verbatim. The data were analysed using thematic analysis. RESULTS: Three overarching themes were identified: (1) enablers and barriers to recruitment and enrolment of patients in RRCTs, (2) experiences of patients participating in RRCTs, and (3) recommendations for the implementation of future RRCTs. For patients, altruism and "trust in the clinician" were key reasons to participate in a RRCT. For clinicians and clinical trial coordinators, the RRCT study design was perceived as "simple and straightforward" but "less exciting" than RCTs. Competition from commercially sponsored RCTs poses challenges for investigator-led RRCTs recruitment, particularly if eligible patient numbers are low. There were limited impacts on patients' treatment experiences and clinicians' clinical workflow given that the RRCTs explored different standards of care. Recommendations to improve the enrolment of patients in RRCTs included generating greater buy-in from clinicians by increasing awareness of RRCTs via education initiatives and broader promotion of the "selling point" of RRCTs and providing monetary compensation to hospitals for enrolling patients. CONCLUSIONS: Whilst patients, clinicians, and study coordinators were generally supportive of RRCTs, several barriers to effective RRCT implementation in oncology were identified. Developing strategies to increase acceptance of the methodology by clinicians will help enhance the uptake of RRCTs in Australia and internationally.


Assuntos
Neoplasias , Humanos , Estudos de Viabilidade , Pesquisa Qualitativa , Sistema de Registros , Neoplasias/diagnóstico , Neoplasias/terapia , Pesquisadores , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Breast Cancer Res Treat ; 198(1): 67-74, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36624321

RESUMO

PURPOSE: Dual anti-HER2 targeted therapy and chemotherapy is the current first-line standard of care for HER2 + metastatic breast cancer (MBC), with endocrine therapy (ET) the backbone of treatment in hormone receptor positive (HR +) disease. The potential ET benefit in HER2 + /HR + patients is unknown as pivotal dual anti-HER2 clinical trials precluded ET use. METHODS: Real-world data from a multi-site registry of consecutive HER2 + MBC patients treated at clinician discretion were examined. Patients that were HR + (ER + and/or PR +) and had received first-line chemotherapy alongside trastuzumab and pertuzumab were explored. Of 362 patients in the registry, 215 were excluded due to being HR- (n = 210) or not receiving chemotherapy (n = 5). RESULTS: Of the 147 patients included, 91 (62%) received concurrent ET and 56 (38%) had not. Comparing the groups, there were no significant differences in age, performance status, metastatic sites, use of previous therapy and de novo metastatic disease. More patients with ER + PR + disease versus those with ER + PR- or ER-PR + received ET (73 vs 45%). The addition of ET was associated with significantly improved 5-year PFS (HR 0.58, CI 0.37-0.89, p = 0.014) and OS (HR 0.52, CI 0.31-0.90, p = 0.018), with no increase in adverse events noted. CONCLUSION: The addition of ET to first-line dual anti-HER2 therapy post chemotherapy in patients with HER2 + /HR + MBC was associated with major gains in PFS and OS with no safety concerns evident. Further studies of this combination are justified, along with studies of how best to integrate other agents that are active in this patient subset, including CDK4/6 inhibitors.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2 , Trastuzumab , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
6.
Cancers (Basel) ; 14(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36077668

RESUMO

Traditional cancer registries have often been siloed efforts, established by single groups with limited objectives. There is the potential for registry data to support a broad range of research, audit and education initiatives. Here, we describe the establishment of a series of comprehensive cancer registries across the spectrum of common solid cancers. The experience and learnings of each registry team as they develop, implement and then use collected data for a range of purposes, that informs the conduct and output of other registries in a virtuous cycle. Each registry is multi-site, multi-disciplinary and aims to collect data of maximal interest and value to a broad range of enquiry, which would be accessible to any researcher with a high-quality proposal. Lessons learnt include the need for careful and continuous curation of data fields, with regular database updates, and the need for a continued focus on data quality. The registry data as a standalone resource has supported numerous projects, but linkage with external datasets with patients in common has enhanced the audit and research potential. Multiple projects have linked registry data with matched tissue specimens to support prognostic and predictive biomarker studies, both validation and discovery. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly randomised studies exploring the optimal use of available therapy options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data.

7.
JAMA Oncol ; 8(11): 1559-1560, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35980644

RESUMO

This Viewpoint examines chemotherapy at the end of life as a quality metric.


Assuntos
Benchmarking , Indicadores de Qualidade em Assistência à Saúde , Humanos
8.
BMC Cancer ; 22(1): 604, 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35655179

RESUMO

BACKGROUND: Real-world data (RWD) is increasingly being embraced as an invaluable source of information to address clinical and policy-relevant questions that are unlikely to ever be answered by clinical trials. However, the largely unrealised potential of RWD is the value to be gained by supporting prospective studies and translational research. Here we describe the design and implementation of an Australian brain cancer registry, BRAIN, which is pursuing these opportunities. METHODS: BRAIN was designed by a panel of clinicians in conjunction with BIOGRID to capture comprehensive clinical data on patients diagnosed with brain tumours from diagnosis through treatment to recurrence or death. Extensive internal and external testing was undertaken, followed by implementation at multiple sites across Victoria and Tasmania. RESULTS: Between February 2021 and December 2021, a total of 350 new patients from 10 sites, including one private and two regional, were entered into BRAIN. Additionally, BRAIN supports the world's first registry trial in neuro-oncology, EX-TEM, addressing the optimal duration of post-radiation temozolomide; and BioBRAIN, a dedicated brain tumour translational program providing a pipeline for biospecimen collection matched with linked clinical data. CONCLUSIONS: Here we report on the first data collection effort in brain tumours for Australia, which we believe to be unique worldwide given the number of sites and patients involved and the extent to which the registry resource is being leveraged to support clinical and translational research. Further directions such as passive data flow and data linkages, use of artificial intelligence and inclusion of patient-entered data are being explored.


Assuntos
Inteligência Artificial , Neoplasias Encefálicas , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Coleta de Dados , Humanos , Estudos Prospectivos , Sistema de Registros , Vitória
10.
Asia Pac J Clin Oncol ; 18(5): e363-e368, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35073441

RESUMO

BACKGROUND: RAS mutation testing now routinely informs the optimal management of metastatic colorectal cancer (mCRC), specifically the finding of a RAS mutation defines patients who will not benefit from treatment with an epidermal growth factor receptor inhibitor. Over time more RAS genes have been tested and more sensitive techniques used. AIMS: To review routine care RAS testing and results over time. METHODS: A retrospective analysis of the molecular data collected prospectively in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry from 2009 to 2018 was undertaken. Patients with RAS data were further analyzed. In parallel, the RAS mutation status of patients enrolled in the Test Tailor Treat (TTT) program was examined for 2011-2018. RESULTS: Of 2908 patients in the TRACC registry, 1892 (65%) were tested, with 898 (47%) of tested patients found to be RAS mutant (RASmt). RAS data were available for 5935 TTT patients. Of the tested TRACC patients diagnosed in 2009 and 2010, 38% were RASmt. For each 2-year period from 2011/2012 through to 2017/2018, the prevalence of RASmt in TRACC and TTT was 42% and 40% (2011/2012), 52% and 40% (2013/2014), 47% and 49% (2015/2016), and 47% and 49% (2017/2018). CONCLUSIONS: Based on both TRACC and TTT data, the proportion of patients reported to have a RAS mutation increased from 2009 to 2015 but has remained relatively stable in recent years. The increased proportion of RASmt patients observed over time is likely largely driven by the uptake of extended RAS testing.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Austrália , Neoplasias do Colo/genética , Neoplasias Colorretais/patologia , Receptores ErbB/genética , Genes ras/genética , Humanos , Mutação , Recidiva Local de Neoplasia , Estudos Retrospectivos
11.
Cancers (Basel) ; 13(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34830967

RESUMO

Despite the high prevalence of prostate cancer in older men, the predictive value of a polygenic risk score (PRS) remains uncertain in men aged ≥70 years. We used a 6.6 million-variant PRS to predict the risk of incident prostate cancer in a prospective study of 5701 men of European descent aged ≥70 years (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. The study endpoint was prostate cancer, including metastatic or non-metastatic disease, confirmed by an expert panel. After excluding participants with a history of prostate cancer at enrolment, we used a multivariable Cox proportional hazards model to assess the association between the PRS and incident prostate cancer risk, adjusting for covariates. Additionally, we examined the distribution of Gleason grade groups by PRS group to determine if a higher PRS was associated with higher grade disease. We tested for interaction between the PRS and aspirin treatment. Logistic regression was used to independently assess the association of the PRS with prevalent (pre-trial) prostate cancer, reported in medical histories. During a median follow-up time of 4.6 years, 218 of the 5701 participants (3.8%) were diagnosed with prostate cancer. The PRS predicted incident risk with a hazard ratio (HR) of 1.52 per standard deviation (SD) (95% confidence interval (CI) 1.33-1.74, p < 0.001). Men in the top quintile of the PRS distribution had an almost three times higher risk of prostate cancer than men in the lowest quintile (HR = 2.99 (95% CI 1.90-4.27), p < 0.001). However, a higher PRS was not associated with a higher Gleason grade groups. We found no interaction between aspirin treatment and the PRS for prostate cancer risk. The PRS was also associated with prevalent prostate cancer (odds ratio = 1.80 per SD (95% CI 1.65-1.96), p < 0.001).While a PRS for prostate cancer is strongly associated with incident risk in men aged ≥70 years, the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease.

12.
Eur J Cancer ; 157: 301-305, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34555649

RESUMO

Countless biomarkers continue to be identified and analysed in the modern era of omics focused research, with innumerable articles purporting clinical utility and bolstering optimism for truly personalised cancer care. While many commentaries have expounded on the complexities of biomarker development, validation and reporting, the monumental challenge of integrating this research into clinical practice has to date received little attention. The challenges are multitude; variable and sometimes contradictory findings across studies for individual biomarkers, a rapidly evolving landscape with new biomarkers continually being presented and tendency to examine each biomarker in isolation. Here, using examples from colorectal cancer, we explore the difficulties for the practicing clinician in interpreting and integrating novel biomarkers. Here, we present the '4Cs' to interrogate the biomarker literature, including analysis of the credibility, consistency, completeness and context of the biomarker research, and suggest a framework to frame the literature moving forward.


Assuntos
Biomarcadores Tumorais/análise , Pesquisa Biomédica/estatística & dados numéricos , Neoplasias Colorretais/terapia , Prestação Integrada de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Confiabilidade dos Dados , Prestação Integrada de Cuidados de Saúde/tendências , Humanos , Padrões de Prática Médica/tendências
13.
Cancers (Basel) ; 13(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34298747

RESUMO

Genomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged 40-69 years. Prospective studies of older women aged ≥70 years have been limited. We assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6339 older women aged ≥70 years (mean age 75 years) enrolled into the ASPREE trial, a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. We evaluated incident BC diagnoses over a median follow-up time of 4.7 years. A multivariable Cox regression model including conventional BC risk factors was applied to prospective data, and re-evaluated after adding the PRS. We also assessed the association of rare pathogenic variants (PVs) in BC susceptibility genes (BRCA1/BRCA2/PALB2/CHEK2/ATM). The PRS, as a continuous variable, was an independent predictor of incident BC (hazard ratio (HR) per standard deviation (SD) = 1.4, 95% confidence interval (CI) 1.3-1.6) and hormone receptor (ER/PR)-positive disease (HR = 1.5 (CI 1.2-1.9)). Women in the top quintile of the PRS distribution had over two-fold higher risk of BC than women in the lowest quintile (HR = 2.2 (CI 1.2-3.9)). The concordance index of the model without the PRS was 0.62 (95% CI 0.56-0.68), which improved after addition of the PRS to 0.65 (95% CI 0.59-0.71). Among 41 (0.6%) carriers of PVs in BC susceptibility genes, we observed no incident BC diagnoses. Our study demonstrates that a PRS predicts incident BC risk in women aged 70 years and older, suggesting potential clinical utility extends to this older age group.

15.
Acta Oncol ; 60(9): 1106-1113, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34184594

RESUMO

BACKGROUND: Multiple meta-analyses have demonstrated that routine surveillance following colorectal cancer surgery improves survival outcomes. There is limited data on how recurrence patterns and post-recurrence outcomes vary by individual tumor stage. METHODS: Using a multi-site community cohort study, we examined the potential impact of primary tumor stage on the sites of recurrence, management of recurrent disease with curative intent, and post-resection survival. We also explored changes over time. RESULTS: Of 4257 new colon cancers diagnosed 2001 through 2016, 789 (21.1%) had stage I, 1584 (42.4%) had stage II, and 1360 (36.4%) had stage III colon cancer. For consecutive 5-year periods (2001-2005, 2006-2010, 2011-2016), recurrence rates have declined (23.4 vs. 17.1 vs. 13.6%, p < 0.001), however, the resection rates of metastatic disease (29.3 vs. 38.6 vs. 35.0%, p = 0.21) and post-resection 5-year survival (52.0 vs. 51.8 vs. 64.2%, p = 0.12) have remained steady. Primary tumor stage impacted recurrence rate (3.8 vs. 12 vs. 28%, p < 0.0001 for stage 1, 2, and 3), patterns of recurrence, resection of metastatic disease, (50 vs. 42 vs. 30%, p < 0.0001) and post-resection 5-year survival (92 vs. 64 vs. 44%, p < 0.001). CONCLUSION: In this community cohort we defined significant differences in recurrence patterns and post-resection survival by tumor stage, with a diminishing rate of recurrence over time. While recurrence rates were lower with stage I and II disease, the high rate of metastatic disease resection and excellent post-resection outcomes help to justify routine surveillance in these patients.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Estudos de Coortes , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/patologia , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
16.
Future Oncol ; 15(25): 2955-2965, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31424262

RESUMO

The initial management of locally advanced rectal cancer continues to evolve and formulating the ideal treatment plan remains challenging, with a multitude of emerging treatment strategies and either limited or inconsistent data to support these. The main objective of neoadjuvant treatment is to maximize disease control and minimize toxicity and impact on quality of life. Ultimately, the optimal approach needs to be personalized to the individual. In this Review, we discuss the various strategies currently used and being further investigated in the initial treatment of patients presenting with locally advanced rectal cancer. We describe the evidence behind the current standard of care recommendations and emerging new options, as well as potential biomarkers that may assist with further refining treatment selection.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Quimiorradioterapia/métodos , Terapia Combinada , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Oxaliplatina/uso terapêutico , Qualidade de Vida , Radioterapia Adjuvante/métodos , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Análise de Sequência de DNA
18.
Future Oncol ; 14(26): 2725-2739, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30004261

RESUMO

While mismatch repair (MMR) deficiency has been studied extensively, the assessment of MMR status in colorectal and other cancers remains highly relevant, particularly in light of recent data demonstrating that MMR deficiency is a strong predictor for treatment benefit with immune checkpoint inhibitors across multiple tumor types. In colorectal cancer, there is a growing consensus in support of routine MMR testing for Lynch syndrome screening, to inform prognosis and adjuvant chemotherapy use in early stage disease, and to predict response to immunotherapy in advanced disease. Here, we provide a review of the Ventana MMR Immunohistochemistry Panel, which was recently approved by the US FDA for use in Lynch syndrome screening.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Reparo de Erro de Pareamento de DNA/genética , Testes Genéticos/métodos , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica/métodos , Programas de Rastreamento/métodos , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
19.
Asia Pac J Clin Oncol ; 14(6): 365-373, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29947051

RESUMO

Substantial progress has recently been made in optimizing the management of cancer patients, resulting in major gains in survival and quality of life. Much of this progress has resulted from the serial testing of promising treatment strategies, typically using prospective randomized controlled trials to compare outcomes achieved with the new approach versus the current standard(s) of care. However, there is an ever-expanding list of important questions that are difficult to investigate, particularly with respect to determining the optimal sequencing and combination of proven active agents. With the rapidly growing list of clinical, pathologic and molecular characteristics that promise to predict treatment benefit and/or risk for defined patient subsets, many new questions regarding how best to personalize our approach to treatment selection are emerging. These questions can be investigated in the context of registry-based randomized clinical trials. Recently, the potential of registry-based randomized clinical trials was demonstrated in cardiology, highlighting the ability to rapidly recruit large numbers of patients to a trial addressing an important clinical question, with minimal cost and high external validity. In this review, we discuss the challenges and limitations of conventional clinical trials in multidisciplinary cancer care, describe the potential advantages of registry-based randomized trials, and highlight several registry-based oncology studies that are already underway to demonstrate the feasibility of this approach.


Assuntos
Projetos de Pesquisa Epidemiológica , Oncologia , Neoplasias/terapia , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sistema de Registros/estatística & dados numéricos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos
20.
J Neurooncol ; 136(1): 155-162, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29079955

RESUMO

Glioblastoma has a poor prognosis with median survival of 12-14 months. Long-term survivors (LTS), alive at least 2 years from diagnosis, comprise 13% of this population. This study aims to provide a clinical profile of LTS at two institutions in Melbourne, Australia. Histological diagnosis of glioblastoma from 1st January 2006 to 31st December 2012 were identified from pathology/oncology databases. Demographic, treatment and survival characteristics were recorded (follow-up to 31st December 2015). Relevant inter-group statistics were used to identify differences between LTS and those surviving less than 2 years. Survival estimated by Kaplan-Meier. 776 patients were identified with 154 surviving > 2 years. Compared with patients surviving < 2 years, LTS were more likely to be younger (median age 56 vs. 65 years, p < .001), have ECOG 0-2 (97 vs. 65%, p < .001), gross tumour resection (91 vs. 61%, p < .001), and receive chemoradiotherapy (94 vs. 40%, p < .001). Most common presenting symptoms amongst LTS were headache (42%), seizure (28%) and speech disturbance (16%). Of LTS, 111 patients (72%) progressed at a median of 20.1 months from diagnosis, with 46% undergoing a second craniotomy. The most common non-surgical second line treatments were temozolomide (41%), followed by radiotherapy (12%). One-third of LTS received three or more lines of treatment, and 10% underwent three or more craniotomies. LTS of glioblastoma (20%) are more likely to be younger, have unilateral tumours, good performance status and undergo multimodality treatment. These data may assist in predicting LTS at diagnosis and understanding their clinical journey to facilitate planning of treatment and supportive care.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Glioblastoma/diagnóstico , Glioblastoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sobreviventes , Adulto Jovem
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