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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.
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Inteligencia Artificial , Neoplasias Encefálicas , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/terapia , Recolección de Datos , Humanos , Estudios Prospectivos , Sistema de Registros , VictoriaRESUMEN
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.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiología , Glioblastoma/diagnóstico , Glioblastoma/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sobrevivientes , Adulto JovenRESUMEN
Over half of glioblastoma (GBM) cases are diagnosed in patients older than 65 years. Their median overall survival (OS) is 4-5 months, compared with 12-14 months in patients younger than 70 years. This retrospective audit aims to identify patterns of care and survival of patients diagnosed with GBM at a single institution in Melbourne, Australia. Consecutive histological diagnoses of adult primary GBM from January 2010 to December 2012 were retrospectively identified from medical records. Demographic, treatment and survival characteristics were recorded until death, with follow-up to January 1st 2015. Survival was estimated by Kaplan-Meier method. Planned, sub-group analyses were conducted using multivariate Cox proportional hazards model to identify differences between elderly and younger cohorts, as well as ECOG. 165 patients were identified (36 % aged ≥70 years). Those ≥70 years had a poorer performance status (ECOG 3-4: 27 vs 10 %, p = .005); poorer median OS (2.6 vs 11.5 months, p < .001); and were less likely to receive adjuvant treatment (no treatment: 40 vs 16 %, p < .001) compared with patients <70 years. Age was not a significant predictor of poorer os (HR 1.0; 0.99-1.03; p > .05), after adjusting for other clinical factors. Significant predictors of poorer os were poor performance status (p = .001), bilateral tumours (p = .04), biopsy only (p = .001), and no adjuvant treatment (p < .001). In patients diagnosed with GBM, those older than 70 years often present with poor performance status, are less likely to receive adjuvant treatment and have inferior os compared with younger patients. Treatment recommendations should be based on performance status/fitness, not age alone.
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Envejecimiento , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Glioblastoma/diagnóstico , Glioblastoma/mortalidad , Sobrevida , Adulto , Factores de Edad , Anciano , Encéfalo/patología , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: People with cancer attend emergency departments (EDs) for many reasons. Improved understanding of the specific needs of these patients may assist in optimizing health service delivery. ED presentation and hospital utilization characteristics were explored for people with cancer and compared with those patients without cancer. METHODS: This descriptive, retrospective, multicentre cohort study used hospital administrative data. Descriptive and inferential statistics were used to summarise and compare ED presentation characteristics amongst cancer and non-cancer groups. Predictive analyses were used to identify ED presentation features predictive of hospital admission for cancer patients. Outcomes of interest were level of acuity, ED and inpatient length of stay, re-presentation rates and admission rates amongst cancer patients and non-cancer patients. RESULTS: ED (529,377) presentations occurred over the 36 months, of which 2.4% (n = 12,489) were cancer-related. Compared with all other attendances, cancer-related attendances had a higher level of acuity, requiring longer management time and length of stay in ED. Re-presentation rates for people with cancer were nearly double those of others (64 vs 33%, p < 0.001), with twice the rate of hospital admission (90 vs 46%, p < 0.001), longer inpatient length of stay (5.6 vs 2.8 days, p < 0.001) and had higher inpatient mortality (7.9 vs 1.0%, p < 0.001). Acuity and arriving by ambulance were significant predictors of hospital admission, with cancer-related attendances having ten times the odds of admission compared to other attendances (OR = 10.4, 95% CI 9.8-11.1). CONCLUSIONS: ED presentations by people with cancer represent a more urgent, complex caseload frequently requiring hospital admission when compared to other presentations, suggesting that for optimal cancer care, close collaboration and integration of oncology, palliative care and emergency medicine providers are needed to improve pathways of care.
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Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Neoplasias/terapia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento , Victoria , Adulto JovenRESUMEN
The long-term survival of patients with adult high-grade glioma (HGG) remains poor, but for those who do live longer functional status and neurocognitive ability may be influenced by residual or recurrent tumour, or treatment-related complications. The aim of this review was to examine the current literature regarding the quality of life and experience of patients living longer with adult HGG and their caregivers, with a view to understanding the burden of treatment on patient abilities and deficits over time. Medline, PsychINFO and CINAHL databases were searched for the core concept of HGG in combination with an aspect of quality of long-term survival. Key findings of the 12 included studies were identified and synthesised thematically. There is a paucity of dedicated studies which have investigated the experiences of this cohort. The strength of existing literature is limited by the systematic exclusion of the poorest functioning patients and the under-representation of caregiver perspectives. Discrepancies in how patients view their quality of life were highlighted, despite consistent findings of significant physical and functional impairment. This review confirmed the presence of important differences between patient and caregiver views regarding patient abilities following treatment. Caregiver burden was found to be high, due to multiple dynamic and relentless stressors. The true experience of patients living longer with adult HGG and their caregivers remains unclear, particularly for patients with poorer neurocognitive and functional outcomes. Further research is required to clarify and replicate findings, explore discrepancies between patient and caregiver views, and to specifically investigate how caregiver needs and experiences may evolve over time.
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Adaptación Psicológica , Neoplasias Encefálicas/psicología , Cuidadores/psicología , Glioma/psicología , Calidad de Vida , Actividades Cotidianas , Adulto , Humanos , Clasificación del Tumor , Pronóstico , Factores de TiempoRESUMEN
Despite being eligible, only 26 patients with primary brain cancer became organ donors from 2009 to 2018 in Australia. We describe two patients with high grade gliomas who successfully donated their organs after obtaining first-person consent in the outpatient setting by careful multidisciplinary planning and an elective intensive care unit admission for organ donation. Barriers and facilitators were examined based on these experiences and suggestions for future practices are explored. The recommended practices include: 1. Systematic incorporation of organ donation into advance care planning. 2. Integrating organ donation organisation coordinators into advance care planning. 3. Standardization of donor care and clear communication and collaboration between treatment teams. 4. Support and involvement of the medical treatment decision maker. 5. Identification of clinical triggers for admission to hospital and intensive care unit. These two cases illustrate that with careful coordination and involvement from a multidisciplinary team, successful organ transplantation outcomes are possible.
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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.
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Exactitud de los Datos , Sistema de Registros , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/terapia , Registro Médico Coordinado/métodos , Anciano de 80 o más Años , Pronóstico , Almacenamiento y Recuperación de la InformaciónRESUMEN
OBJECTIVES: Symptoms of raised intracranial pressure (ICP) in recurrent high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on ICP symptoms. Acetazolamide reduces ICP when used in other clinical non-cancer settings. The aim of the study was to explore whether the addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent HGG. METHODS: Participants had recurrent HGG with any of dexamethasone recommencement, dose increase or dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide or placebo for 8 weeks. Standardised protocols were used for dexamethasone dosing, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stable Karnofsky Performance Status Secondary endpoints included toxicity and feasibility. RESULTS: Thirty participants (15 per group) were enrolled (mean age 58 years) from seven Australian sites. The mean baseline dexamethasone dose was 6.2 mg. Mean duration on study treatment was 38 days (placebo group) and 31 days (acetazolamide group) with nine participants (30%) completing all study treatments (six placebo, three acetazolamide). Study withdrawal was due to adverse events (n=6; one placebo, five acetazolamide) and disease progression (n=6 (three per arm)). Four participants (13%) (two per arm) were stable responders. Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: five participants (33%), six events, two related). CONCLUSIONS: The study closed early due to poor accrual and increasing availability of bevacizumab. The addition of acetazolamide did not facilitate dexamethasone reduction. TRIAL REGISTRATION NUMBER: ACTRN12615001072505.
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Edema Encefálico , Glioma , Humanos , Persona de Mediana Edad , Acetazolamida/uso terapéutico , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Bevacizumab , Método Doble Ciego , Recurrencia Local de Neoplasia/tratamiento farmacológico , Australia , Glioma/complicaciones , Glioma/tratamiento farmacológico , Dexametasona/uso terapéuticoRESUMEN
INTRODUCTION: Glioblastoma (GBM) is the most common malignant primary central nervous system cancer in adults. The objective of the Multi-Arm GlioblastoMa Australasia (MAGMA) trial is to test hypotheses in real world setting to improve survival of people with GBM. Initial experimental arms are evaluating the effectiveness of interventions in newly diagnosed GBM (ndGBM). This study will compare maximal surgical resection followed by chemoradiotherapy plus adjuvant chemotherapy for 6 months with the addition of (1) 'neoadjuvant' chemotherapy beginning as soon as possible after surgery and/or (2) adjuvant chemotherapy continued until progression within the same study platform. METHODS AND ANALYSIS: MAGMA will establish a platform for open-label, multiarm, multicentre randomised controlled testing of treatments for GBM. The study began recruiting in September 2020 and recruitment to the initial two interventions in MAGMA is expected to continue until September 2023.Adults aged ≥18 years with ndGBM will be given the option of undergoing randomisation to each study intervention separately, thereby giving rise to a partial factorial design, with two separate randomisation time points, one for neoadjuvant therapy and one for extended therapy. Patients will have the option of being randomised at each time point or continuing on with standard treatment.The primary outcome for the study is overall survival from the date of initial surgery until death from any cause. Secondary outcomes include progression-free survival, time to first non-temozolomide treatment, overall survival from each treatment randomisation, clinically significant toxicity as measured by grade 3 or 4 adverse events and health-related quality-of-life measures. Tertiary outcomes are predictive/prognostic biomarkers and health utilities and incremental cost-effectiveness ratio.The primary analysis of overall survival will be performed separately for each study intervention according to the intention to treat principle on all patients randomised to each study intervention. ETHICS AND DISSEMINATION: The study (Protocol version 2.0 dated 23 November 2020) was approved by a lead Human Research Ethics Committee (Sydney Local Health District: 2019/ETH13297). The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBER: ACTRN12620000048987.
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Glioblastoma , Adolescente , Adulto , Australasia , Quimioradioterapia , Quimioterapia Adyuvante , Glioblastoma/terapia , Humanos , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIM: Evaluation of the Nativis Voyager®, an investigational medical device, as monotherapy for recurrent glioblastoma (rGBM). MATERIALS & METHODS: A total of 15 patients with rGBM were treated with one of two Voyager ultra-low radio frequency energy cognates: A1A or A2HU. Safety and clinical utility were assessed every 2-4 months. RESULTS: Median overall survival was 8.04 months in the A1A arm and 6.89 months in the A2HU arm. No serious adverse events associated with Voyager were reported. No clinically relevant trends were noted in clinical laboratory parameters or physical exams. CONCLUSION: The data suggest that the Voyager is safe and feasible for the treatment of rGBM.
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Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Magnetoterapia , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Australia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Estudios de Factibilidad , Femenino , Glioblastoma/diagnóstico por imagen , Glioblastoma/mortalidad , Humanos , Magnetoterapia/instrumentación , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/mortalidad , Resultado del TratamientoRESUMEN
AIM: Targeted therapy (TT) has improved survival for metastatic renal cell carcinoma (mRCC). However, survival is usually limited if brain metastases (BMs) develop. We aimed to evaluate survival outcomes in mRCC patients based on timing of BM diagnosis. METHODS: We conducted a multicenter, retrospective study of mRCC patients with BM who received TT at any point between 2005 and 2014. We determined overall survival (OS) from stage IV diagnosis, TT initiation and BM diagnosis, and prognostic factors. Patients were grouped into three categories: synchronous-BM, metachronous-BM diagnosed while conservatively managed (metachronous-BM before TT) and metachronous-BM diagnosed during TT. Survival was calculated by Kaplan-Meier method and predictors were calculated using Cox hazards regression. RESULTS: Incidence of BM was 17% in mRCC patients treated with TT (two centers). Fifty-four mRCC-BM patients were identified from five tertiary centers. Twenty-eight percentage (15/54) had synchronous-BM, 28% (15/54) had metachranous-BM before TT and 44% (24/54) had metachronous-BM during TT. Most had central nervous system (CNS) symptoms at BM diagnosis (78%; 42/54). Median OS from stage IV diagnosis, TT commencement and BM diagnosis was 28 months (95% confidence interval [CI] 16-43), 19 months (95% CI 9-26) and 9 months (95% CI 5-16), respectively. Synchronous-BM group trended toward poorer survival from TT commencement (P = 0.06). Metachronous-BM during TT group had lower survival from BM diagnosis than synchronous-BM and metachronous-BM before TT group (P < 0.001). Eight of 50 deaths (16%) were from neurological complications. The presence of CNS symptoms did not predict worse survival from stage IV diagnosis (P = 0.73). CONCLUSION: In patients with mRCC, the development of BM while on TT portends shorter prognosis compared with synchronous diagnosis of BM at stage IV disease or metachronous BM developed prior to commencing TT. The presence of CNS symptoms does not predict worse survival.
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Neoplasias Encefálicas/mortalidad , Carcinoma de Células Renales/mortalidad , Neoplasias Renales/mortalidad , Terapia Molecular Dirigida , Tiempo de Tratamiento , Australia/epidemiología , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Femenino , Humanos , Neoplasias Renales/patología , Neoplasias Renales/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Palliative chemotherapy has an increasing role in the management of recurrent high-grade gliomas. Temozolomide is a well-tolerated agent that results in objective responses and stabilisation of disease. Theoretically, temozolomide may be more effective when given in a prolonged schedule rather than the standard 5 days-monthly schedule. This Phase II study examined the efficacy and toxicity of temozolomide when given in a two-weekly schedule. Twenty-five patients received 150 mg/m2 temozolomide daily for seven days alternating with seven days of no treatment. One cycle of temozolomide was a total of two weeks treatment in every 28 days. Of the 25 evaluable patients, there was one complete response (4%), four partial responses (16%) and 10 patients had disease stablisation (40%). The progression free survival at 6 months was 56%. Two-weekly temozolomide was well tolerated with only four episodes of Grade 3 thrombocytopenia. Overall, two-weekly temozolomide is an active and well tolerated schedule, but does not appear to improve on the activity of temozolomide using the standard 5-day schedule.
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Antineoplásicos Alquilantes/uso terapéutico , Dacarbazina/análogos & derivados , Glioma/tratamiento farmacológico , Adulto , Anciano , Dacarbazina/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Evaluación de Medicamentos , Femenino , Glioma/clasificación , Humanos , Masculino , Persona de Mediana Edad , Temozolomida , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: The benefits of recording the tumor, node, and metastasis (TNM) stages of cancer patients are well accepted, but little is known about how accurately this is performed. An audit was performed to determine the accuracy of recorded stage and to act as a baseline before the implementation of an education program. PATIENTS AND METHODS: All new patient referrals to Princess Margaret Hospital between July 1 and August 31, 1997, were reviewed. An audit panel composed of five health record technicians (HRTs) and 10 doctors was assembled. Each auditor reviewed 10% of the health record. If there was a discrepancy between the stage in the health record and the auditor stage, then the final stage was determined by the audit committee. Analysis of the agreement between the health record, the physician auditor, the HRT auditor, and the final stage was performed. RESULTS: A total of 855 patients were referred with a new diagnosis of a malignancy for which there was a TNM stage system; 833 patients (97.4%) had a stage assigned. There was agreement between the health record stage and final stage in 80% (95% confidence interval [CI], 77% to 82%) of cases for clinical stage, compared with 90% (95% CI, 87% to 92%) for pathologic stage. Of the major site groups, lung was the least accurately recorded. The most common major discrepancies were due to the recording of X when a definite category could be assigned. CONCLUSION: This audit demonstrates the importance of staging and provides impetus to develop staging guidelines and education programs.
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Instituciones Oncológicas/normas , Auditoría Médica , Registros Médicos/normas , Metástasis de la Neoplasia , Estadificación de Neoplasias , Control de Formularios y Registros , Humanos , Neoplasias Pulmonares , Derivación y Consulta , Reproducibilidad de los ResultadosRESUMEN
UNLABELLED: This paper details the case of a 77-year-old male with refractory hypoglycaemia due to inoperable metastatic pancreatic neuroendocrine tumour (pNET) co-secreting insulin and gastrin. Multiple medical therapies were trialled with limited success, and we describe the complications experienced by our patient. Somatostatin analogues can ameliorate hypoglycaemia and may have tumour-stabilising effects; however, in our case resulted in paradoxical worsening of hypoglycaemia. This rendered our patient hospital dependent for glycaemic support including continuous dextrose infusion. Although this is a reported adverse effect with initiation of therapy, we describe successful initiation of short-acting octreotide as an inpatient followed by commencement of long-acting octreotide. Hypoglycaemic collapse occurred only after dose titration of long-acting octreotide. We outline the pitfalls of somatostatin analogue therapy and the mechanisms that may contribute to worsening hypoglycaemia. This rare side effect cannot be reliably predicted, necessitating close supervision and glucose monitoring during therapy. Our patient achieved disease stabilisation and gradual resolution of hypoglycaemia with peptide receptor radionuclide therapy (PRRT), an emerging therapeutic option for metastatic neuroendocrine tumours with high efficacy and low toxicity. We present a brief but comprehensive discussion of currently available and novel therapies for insulin secreting pNETs. LEARNING POINTS: Hypoglycaemia due to malignant insulin secreting pNET is frequently severe and may be life-threatening despite supportive therapies.Octreotide can ameliorate hypoglycaemia, and may have anti-proliferative and tumour-stabilising effects in malignant pNETs that are surgically unresectable.Paradoxical worsening of hypoglycaemia may occur with octreotide initiation and dose titration, necessitating close supervision and glucose monitoring.PRRT is emerging as a therapeutic option with high efficacy and low toxicity.
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There is increasing interest in circulating tumor cells (CTCs) due to their purported role in breast cancer metastasis, and their potential as a "liquid biopsy" tool in breast cancer diagnosis and management. There are, however, questions with regards to the reliability and consistency of CTC detection and to the relationship between CTCs and prognosis, which is limiting their clinical utility. There is increasing acceptance that the ability of CTCs to alter from an epithelial to mesenchymal phenotype plays an important role in determining the metastatic potential of these cells. This review examines the phenotypic and genetic variation, which has been reported within CTC populations. Importantly, we discuss how the detection and characterization of CTCs provides additional and often differing information from that obtained from the primary tumor, and how this may be utilized in determining prognosis and treatment options. It has been shown for example that hormone receptor status often differs between the primary tumor and CTCs, which may help to explain failure of endocrine treatment. We examine how CTC status may introduce alternative treatment options and also how they may be used to monitor treatment. Finally, we discuss the most interesting current clinical trials involving CTC analysis and note further research that is required before the breast cancer "liquid biopsy" can be realized.
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Temozolomide has established activity in the treatment of recurrent glioblastoma multiforme (GBM). Caelyx (liposomal doxorubicin) has established activity in a broad range of tumors but has not been extensively evaluated in the treatment of GBM. Phase 1 data suggest that temozolomide and Caelyx can be combined safely at full dose. In this phase 2 study, combination temozolomide (200 mg/m(2) orally, days 1-5) and Caelyx (40 mg/m(2) i.v., day 1) was given every 4 weeks to a cohort of 22 patients with recurrent GBM, who received a total of 109 cycles (median 3.5 cycles). The median age of the patients was 55 years (range, 31-80 years), and 17 were male. All patients had received radiotherapy, but only 2 had received prior chemotherapy. One patient (5%) had a complete response, 3 patients (14%) had a partial response, and 11 patients (50%) had stable disease. The median time to progression for the cohort was 3.2 months (range, 1-13 months). Median overall survival was 8.2 months (range, 1-16+ months). Seven patients (32%) were progression free at 6 months. Hematological toxicity included grade 3/4 neutropenia in 4 patients (18%) and grade 3/4 thrombocytopenia in 4 patients (18%). Grade 3 non-hematologic toxicity included rash in 3 patients (14%), nausea and vomiting in 1 patient (4%), hypersensitivity reaction to Caelyx in 3 patients (14%), and palmar-plantar toxicity in 1 patient (4%). We conclude that the combination of temozolomide and Caelyx is well tolerated, results in a modest objective response rate, but has encouraging disease stabilization in the treatment of recurrent GBM.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Dacarbazina/análogos & derivados , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Intervalos de Confianza , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , TemozolomidaRESUMEN
AIM: To examine the relationship between changes in serum carcinoembryonic antigen (CEA) levels and survival during oxaliplatin-based chemotherapy for metastatic colorectal cancer (mCRC). METHODS: A retrospective review of 142 patients with mCRC who were treated with oxaliplatin-based chemotherapies (mostly FOLFOX 6 or XELOX) by St Vincent's Hospital, from October 1999 until 30 November 2007. Survival analysis was used to determine median overall survival (OS) from commencement of chemotherapy. A CEA response was defined by ≥50% decline compared with baseline, maintained on two consecutive occasions at least 4 weeks apart. The Cox proportional hazard model and a landmark analysis at 3 months were used to evaluate survival differences between CEA responders (rCEA) and non-responders (non-rCEA). RESULTS: The median OS was 14.7 months. Using an intention-to-treat analysis, 76 (53.5%) patients achieved a CEA response, while 66 (46.5%) did not. Using the landmark analysis at 3 months, rCEA had a longer survival than non-rCEA (median 16.0 vs 7.8 months, P < 0.0001). The hazard ratio for patients dying of mCRC in non-rCEA was 2.2 (P < 0.0001). In multivariate analysis, CEA response and better baseline Eastern Cooperative Oncology Group (ECOG) predicted for survival (P < 0.0001 for both), while age, gender and histology grade did not. CONCLUSION: The median OS of our patients is similar to published randomized trials. A CEA response of ≥50% at 3 months and good ECOG were independent predictors of OS of patients with mCRC treated with oxaliplatin-based chemotherapies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Estudios de Cohortes , Neoplasias Colorrectales/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Oxaloacetatos , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Concurrent and post-radiotherapy temozolomide (T) significantly improves survival in patient with newly diagnosed glioblastoma multiforme. We aimed to assess the activity of the combination of T and pegylated liposomal doxorubicin (PLD) in this population. A combination of T (days 1-5, 200mg/m(2) orally) and PLD (day 1, 40 mg/m(2) intravenous) was given every 4 weeks for six cycles following chemo-radiotherapy as a post-operative treatment. The primary endpoint was 6-month progression free survival (6PFS). Of the 40 patients who enrolled (53 years median age, 73% male), the 6PFS was 58% (95% confidence interval [CI], 41-72%). The median time to progression was 6.2 months (95% CI, 5.6-8.0 months) and overall survival (OS) was 13.4 months (95% CI, 12.7-15.8 months). Thirty-four patients had measurable disease: one had a complete response (3%), 28 had stable disease (82%), and five had progressive disease (15%). Treatment was well tolerated: hematological toxicity included grade 3 neutropenia (8%). Grade 3 non-hematologic toxicity included nausea and vomiting (8%) and palmar-plantar toxicity (5%). We concluded that combination T and PLD is well tolerated but does not add significant clinical benefit regarding 6PFS and OS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Dacarbazina/análogos & derivados , Doxorrubicina/análogos & derivados , Glioblastoma/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Dacarbazina/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Esquema de Medicación , Femenino , Glioblastoma/mortalidad , Glioblastoma/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Estudios Prospectivos , Tasa de Supervivencia , Temozolomida , Resultado del TratamientoRESUMEN
Glial tumors with oligodendroglial components are considered chemo-responsive. Forty newly diagnosed patients (11 anaplastic oligodendrogliomas [OD] and 29 anaplastic oligoastrocytomas [OA]) were enrolled into this multicenter, open-label, single-arm Phase II trial of first-line temozolomide (200 mg/m(2) on days 1-5 every 4 weeks for 6 cycles). The primary endpoint was 6-month progression-free survival (PFS) with response rate (RR), median PFS, and median overall survival (OS) as secondary endpoints. Of 39 evaluable patients at the 6-month time point (median follow-up, 34 months), 6-month PFS was 77% (95% confidence interval [CI], 74.5%-79.3%). There were 15 complete responses (CRs, 38%), 6 partial responses (PRs, 15%), and 9 disease stabilization (23%). The median PFS was 21 months (95% CI, 3-39 months), and the median OS was 43 months (95% CI, 20-66 months). Chromosome 1p/19q codeletions were seen in 47% (18 of 38) of the patients, and O-6-methylguanine-DNA-methyltransferase (MGMT) methylation was seen in 48% (10 of 21) of the patients. All patients with OD showed MGMT methylation and most (71%) had chromosome 1p/19q codeletions. Conversely, fewer patients with OA showed MGMT methylation (23%) or had chromosome 1p/19q codeletions (31%). The presence of either 1p/19q codeletion or MGMT methylation was associated with increased RR at 6 months but not with improved PFS or OS. Only 18% of the patients (7 of 40) experienced treatment-related grade 3/4 toxicities. This regimen was active and well tolerated. These data add to the growing body of data showing that primary chemotherapy may be an acceptable alternative to radiotherapy for patients with gliomas containing oligodendroglial histology.