RESUMEN
BACKGROUND: Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS: A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS: Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS: EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.
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Edad de Inicio , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Resultado del Tratamiento , Estudios Prospectivos , Adenocarcinoma/terapia , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adenocarcinoma/mortalidadRESUMEN
BACKGROUND: Botulinum toxin, produced by the Gram-positive anaerobe Clostridium botulinum, is composed of seven antigenic subtypes (A, B, C, D, E, F, and G). Currently, only Botulinum toxin type A, commonly referred to as "Botox," is approved for clinical use, given its relatively safe clinical profile. Botulinum toxin type A has a wide range of therapeutic indications, including treatment for dystonia, migraine headache, neurogenic bladder, and large muscle spastic disorders. However, the toxin is most widely known for its cosmetic effects in treating wrinkles and facial lines. CASE PRESENTATION: This article describes a 62-year-old Caucasian female who presented for investigation and workup of an isolated lytic lesion of her frontal bone a few weeks after administration of botulinum toxin injection into the corresponding site in the frontalis muscle. This presented as a large, palpable, painless forehead lump causing significant psychological distress. After no neoplastic cause for the lesion was found and histopathology was performed, our researchers concluded that the most likely explanation was that the bony lytic lesion resulted from inadvertent injection of the "Botox" neurotoxin through the intended target muscle and into the cortex of the underlying bone. CONCLUSIONS: Our search of the literature failed to identify any previous cases of this occurring. However, as the popularity of this cosmetic procedure only increases, we believe that this represents an important possible differential for isolated lytic lesion after administration of "Botox" injection.
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Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Femenino , Humanos , Persona de Mediana Edad , Toxinas Botulínicas Tipo A/efectos adversos , Diagnóstico Diferencial , Cara , Cabeza , Fármacos Neuromusculares/efectos adversosRESUMEN
BACKGROUND: Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis. RESULTS: The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001). CONCLUSIONS: NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Gemcitabina , Estudios Retrospectivos , Desoxicitidina , Fluorouracilo , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Leucovorina , Neoplasias PancreáticasRESUMEN
Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system-level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Técnica Delphi , Indicadores de Calidad de la Atención de Salud , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , AntiviralesRESUMEN
BACKGROUND: First-line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head phase III randomised controlled trials (RCT). Data on optimum first-line treatment and subsequent sequencing is lacking. OBJECTIVE: To compare overall survival (OS) between first-line treatment regimens in a real-world population to determine if an optimal therapeutic sequence is associated with survival benefit. METHODS: A retrospective analysis of prospectively collated data from the Australasian PURPLE pancreatic cancer registry was undertaken. FINDINGS: From 2016 to 2020, of 1551 pancreatic cancer patients, 615 received palliative-intent chemotherapy. Patients with early-stage resected disease without recurrence (n = 369), radiotherapy alone (n = 43), received supportive care alone (n = 458) or had less than 3 months follow-up (n = 66) were excluded. Median OS was comparable between patients receiving first-line Gemcitabine/Nab-Paclitaxel (n = 376) and those receiving FOLFIRINOX (n = 73) (11.3 versus 12.3 months, P = 0.37), with 38% proceeding to second-line chemotherapy which was associated with longer mOS compared to first-line treatment alone (17.4 versus 8.2 months, P < 0.001). With second-line treatment following prior FOLFIRINOX (n = 29) or Gemcitabine/Nab-Paclitaxel (n = 101), mOS did not differ significantly (17.3 versus 15.9 months, P = 0.92), respectively, whilst median progression-free survival was longer with prior FOLFIRINOX (5.2 versus 2.9 months, P = 0.03). CONCLUSION: There was no significant difference in overall survival between either first-line chemotherapy choice, despite patients receiving FOLFIRINOX being younger, fitter, and more likely to have localised disease. However, FOLFIRINOX was associated with delayed progression. In the absence of phase III RCT data, clinicians should be comfortable using either Gemcitabine/Nab-Paclitaxel or FOLFIRINOX as first-line therapy in advanced PDAC.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/patología , Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/análogos & derivados , Fluorouracilo , Humanos , Irinotecán , Leucovorina , Oxaliplatino , Paclitaxel , Neoplasias Pancreáticas/patología , Sistema de Registros , Gemcitabina , Neoplasias PancreáticasRESUMEN
OBJECTIVE: Identifying modifiable factors affecting work ability among cancer survivors is important. The primary aim of the present study was to examine the effects of depression and related psychological factors on work ability among breast cancer survivors in Australia. METHODS: In this cross-sectional electronic and postal survey, Australian breast cancer survivors were investigated. Work status and conditions before and after cancer treatment were analysed. Work ability was measured using the Work Limitation Questionnaire©-Short Form (WLQ-SF) with its four domains (time management, physical tasks, mental-interpersonal tasks, and output tasks). Three psychological factors were investigated: depression, fear of cancer recurrence, and demoralisation. Sociodemographic and clinical data were also collected. Multivariate regression analysis was used to identify the associations of psychological factors with WLQ-SF. RESULTS: Among eligible survivors, 310 (50%) responded to the survey and were analysed. Nearly one third reported their work conditions had changed after cancer treatment. The depressed group reported limited work ability in 35%-44% of the four domains of WLQ-SF, while the non-depressed group reported limited work ability in only 8%-13%. At-work productivity loss was approximately fourfold higher in the depressed group than in the non-depressed group. In multivariate analysis, at-work productivity loss was associated with depression, demoralisation, and past history of anxiety. CONCLUSIONS: After breast cancer treatment, work conditions changed toward lower wages and working hours. Depression, demoralisation, and past history of anxiety were associated with lower work ability. Further evaluations of work rehabilitation in breast cancer survivors are warranted.
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Neoplasias de la Mama , Supervivientes de Cáncer , Ansiedad/epidemiología , Australia , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Supervivientes de Cáncer/psicología , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , Femenino , Humanos , Recurrencia Local de Neoplasia , Calidad de Vida/psicología , Sobrevivientes/psicología , Evaluación de Capacidad de TrabajoRESUMEN
BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is highly lethal. Combination chemotherapy regimens improve overall survival (OS). Historically, only one-third of mPDAC patients in Victoria received chemotherapy. AIM: To describe current Australian chemotherapy utilisation and outcomes in patients with mPDAC using the multi-site PURPLE (Pancreatic cancer: Understanding Routine Practice and Lifting End Results) registry. METHODS: PURPLE collects longitudinal data on consecutive patients with pancreatic cancer seen since January 2016. Data were collated for patients with mPDAC from six Victorian sites, and analysed descriptively. RESULTS: Three hundred and sixty-three patients with mPDAC were identified. Median age was 70 years (range 20-94 years). First-line chemotherapy was administered in 195 (54%) patients. Prevalent regimens included gemcitabine-nab-paclitaxel (71%), gemcitabine alone (10%) and FOLFIRINOX (6%). Sixty-two of 195 (32%) patients who received first line treatment have proceeded to second-line chemotherapy. Chemotherapy-treated patients were younger (69 versus 73 years; P < 0.01), with better Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1 89 vs 66%; P < 0.01) and lower median Charlson comorbidity index (3 vs 4; P < 0.01) compared with untreated patients. Median OS of the entire cohort from diagnosis of metastases was 5.1 months. Median OS was 9.3 months in the chemotherapy treated patients, and 2.5 months in chemotherapy-untreated patients (P < 0.01). CONCLUSIONS: A substantial proportion of patients with mPDAC still do not receive active treatment, which may in part by explained by age, poor performance status and comorbidity. Gemcitabine-nab-paclitaxel was the preferred first-line chemotherapy regimen. Median OS for treated patients in this cohort was comparable to that of recent published clinical trials.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Victoria/epidemiología , Adulto JovenRESUMEN
APR-246 (eprenetapopt) is in clinical development with a focus on hematologic malignancies and is promoted as a mutant-p53 reactivation therapy. Currently, the detection of at least one TP53 mutation is an inclusion criterion for patient selection into most APR-246 clinical trials. Preliminary results from our phase Ib/II clinical trial investigating APR-246 combined with doublet chemotherapy [cisplatin and 5-fluorouracil (5-FU)] in metastatic esophageal cancer, together with previous preclinical studies, indicate that TP53 mutation status alone may not be a sufficient biomarker for APR-246 response. This study aims to identify a robust biomarker for response to APR-246. Correlation analysis of the PRIMA-1 activity (lead compound to APR-246) with mutational status, gene expression, protein expression, and metabolite abundance across over 700 cancer cell lines (CCL) was performed. Functional validation and a boutique siRNA screen of over 850 redox-related genes were also conducted. TP53 mutation status was not consistently predictive of response to APR-246. The expression of SLC7A11, the cystine/glutamate transporter, was identified as a superior determinant of response to APR-246. Genetic regulators of SLC7A11, including ATF4, MDM2, wild-type p53, and c-Myc, were confirmed to also regulate cancer-cell sensitivity to APR-246. In conclusion, SLC7A11 expression is a broadly applicable determinant of sensitivity to APR-246 across cancer and should be utilized as the key predictive biomarker to stratify patients for future clinical investigation of APR-246.
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Sistema de Transporte de Aminoácidos y+/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Mutación , Proteína p53 Supresora de Tumor/genética , Sistema de Transporte de Aminoácidos y+/genética , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Cisplatino/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Fluorouracilo/administración & dosificación , Humanos , Metaboloma , Pronóstico , Proteoma , Quinuclidinas/administración & dosificación , Transcriptoma , Células Tumorales CultivadasRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) presents as unresectable disease in 80% of patients. Limited Australian data exists regarding management and outcome of palliative management for PDAC. This study aims to: (i) identify patients with PDAC being managed with palliative intent; (ii) assess the type of palliative management being used. METHODS: A prospectively maintained pancreatic database at Western Health (2015-2017) was used to identify patient demographics; stage and multidisciplinary decision regarding resectability and operative interventions; palliative care; use of chemotherapy, radiotherapy and; management of exocrine and endocrine insufficiency. Data on chemotherapy use, number of hospital admissions, emergency department attendances and intensive care unit admissions 30 days prior to death were recorded. RESULTS: One-hundred and eleven patients had diagnosis of PDAC, 15% with locally advanced and 45% with metastatic PDAC. Among the locally advanced and metastatic PDAC, 48% received biliary stent insertions, 93% had palliative care referral, 45% received palliative chemotherapy and 10% received radiotherapy. Dietitian referral occurred in 79% and 36% were prescribed with a pancreatic enzyme replacement therapy. Diabetes mellitus was present in 52% of which 31% was new onset. Within 30 days prior to death, 11% patients received palliative chemotherapy, 32% were hospitalized and 11% visited an emergency department more than once. Sixty-five percent died in hospital. CONCLUSION: A high proportion of patients diagnosed with locally advanced and metastatic PDAC received palliative care referrals and appropriate level of end-of-life care. Further prospective studies are necessary, examining the management and impacts of pancreatic insufficiency in this group.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Australia/epidemiología , Humanos , Cuidados Paliativos , Neoplasias Pancreáticas/terapia , Estudios ProspectivosRESUMEN
Immune checkpoint inhibitors (ICIs) have led to major therapeutic advances in the management of malignancy. Despite promising outcomes for some cancers, ICIs are linked to unique side-effects known as immune-related adverse events (IrAEs). These may affect a wide array of organ systems. In particular, ICI-induced hepatitis is diagnostically challenging given its variable natural history and clinical manifestations. The onset of ICI-induced hepatitis often occurs between 6 and 14 weeks after treatment initiation and rarely exhibits delayed presentations or manifests after treatment cessation. We present a case of very delayed-onset ICI-induced hepatitis, stressing the importance of long-term surveillance for immune-indued hepatitis in patients initiated on ICIs even long after treatment cessation.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hepatitis , Neoplasias , Anticuerpos Monoclonales Humanizados/efectos adversos , Hepatitis/diagnóstico , Hepatitis/etiología , HumanosRESUMEN
BACKGROUND: Pancreatic cancer has the highest mortality rate among all main cancer types and is the fourth leading cause of cancer death in Australia. OBJECTIVE: This review focuses on the 95% of pancreatic cancers that arise as pancreatic ductal adenocarcinoma, with the aim to summarise current recommendations for diagnosis and treatment. DISCUSSION: No cardinal symptoms for pancreatic cancer exist. Weight loss combined with abdominal symptoms or back pain in individuals aged ≥60 years prompts urgent computed tomography of the abdomen, while individuals aged ≥40 years with jaundice require direct specialist referral. Pancreatic cancer is categorised as resectable, borderline resectable, locally advanced or metastatic. Resectable disease is treated with surgical resection and adjuvant chemotherapy. Borderline resectable and locally advanced disease are treated with neoadjuvant therapy, followed by surgical exploration if the disease is non-progressive. Metastatic and unresectable disease is treated with chemotherapy or best supportive care. Nutritional support is required for most patients.
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Antineoplásicos/uso terapéutico , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/terapia , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Derivación y Consulta , Factores de Edad , Carcinoma Ductal Pancreático/genética , Quimioterapia Adyuvante , Predisposición Genética a la Enfermedad , Humanos , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Pancreáticas/genética , Factores de RiesgoRESUMEN
PURPOSE: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia. PARTICIPANTS: It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation. FINDINGS TO DATE: The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile. FUTURE PLANS: The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.
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Neoplasias Gastrointestinales/terapia , Sistema de Registros , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Neoplasias del Sistema Biliar/epidemiología , Neoplasias del Sistema Biliar/terapia , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/terapia , Femenino , Neoplasias Gastrointestinales/epidemiología , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/terapia , Mejoramiento de la Calidad , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/terapiaRESUMEN
BACKGROUND: Metastatic colorectal cancer (mCRC) patients with a right-sided primary (RC) have an inferior survival to mCRC arising from a left-sided primary (LC). Previous analyses have suggested multiple factors contribute. METHODS: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry prospectively captured data on consecutive mCRC patients. RC were defined as tumors proximal to the splenic flexure; LC were those at and distal to the splenic flexure and included rectal cancers. Patient, tumor, treatment, and survival data were analyzed stratified by side. RESULTS: Of 2306 patients enrolled from July 2009-March 2018, 747 (32%) had an RC. Patients with RC were older, more likely to be female and have a Charlson score ≥3. RC were more frequently BRAF mutated, deficient in mismatch repair, associated with peritoneal metastases, and less likely to receive chemotherapy. Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1 vs. 10.8 months, hazard ratio [HR] for progression in RC 1.38, P < 0.001). Median overall survival for all RC patients was inferior (19.6 vs. 27.5 months, HR for death in RC 1.44, P < 0.001), and inferior within the treated (21 vs. 29.5 months, HR 1.52, P < 0.001) and untreated subgroups (5.9 vs. 10.3 months, HR 1.38, P = 0.009). Primary side remained a significant factor for overall survival in multivariate analysis. CONCLUSION: Our data from a real-world population confirms the poorer prognosis associated with RC. Primary tumor location remains significantly associated with overall survival even when adjusting for multiple factors, indicating the existence of further side-based differences that are as yet undefined.
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Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: Best practise care optimises survival and quality of life in patients with pancreatic cancer (PC), but there is evidence of variability in management and suboptimal care for some patients. Monitoring practise is necessary to underpin improvement initiatives. We aimed to develop a core set of quality indicators that measure quality of care across the disease trajectory. METHODS: A modified, three-round Delphi survey was performed among experts with wide experience in PC care across three states in Australia. A total of 107 potential quality indicators were identified from the literature and divided into five areas: diagnosis and staging, surgery, other treatment, patient management and outcomes. A further six indicators were added by the panel, increasing potential quality indicators to 113. Rated on a scale of 1-9, indicators with high median importance and feasibility (score 7-9) and low disagreement (<1) were considered in the candidate set. RESULTS: From 113 potential quality indicators, 34 indicators met the inclusion criteria and 27 (7 diagnosis and staging, 5 surgical, 4 other treatment, 5 patient management, 6 outcome) were included in the final set. CONCLUSIONS: The developed indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research in PC care.
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Técnica Delphi , Neoplasias Pancreáticas/terapia , Indicadores de Calidad de la Atención de Salud , Australia , Consenso , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Calidad de VidaRESUMEN
BACKGROUND: Emerging evidence on the optimal use of chemotherapy and biologics in patients with metastatic colorectal cancer should impact management in routine care. Recent studies have demonstrated benefits for initial triplet chemotherapy (5-fluorouracil, oxaliplatin and irinotecan, FOLFOXIRI) and for initial treatment with an epidermal growth factor receptor inhibitor (EGFRi) in patients with a RAS wild-type tumour and a left-sided primary tumour. AIM: To explore evolving pattern of metastatic colorectal cancer care over time in Australia. METHODS: We analysed data from the Treatment of Recurrent and Advanced Colorectal Cancer registry. RESULTS: From July 2009 to December 2017, 2552 metastatic colorectal cancer patients were entered into the Treatment of Recurrent and Advanced Colorectal Cancer registry. Of 1585 patients who initially underwent chemotherapy, treatment was with a doublet in 76%. FOLFOXIRI was given to 22 patients (1.4%), mostly young patients and those with potentially resectable disease. Along with first-line chemotherapy, 61% received bevacizumab, while 3.3% received an EGFRi, predominantly over the last 2 years. Within the KRAS wild-type left-sided tumour cohort, EGFRi use increased from 9% in 2015 to 37% in 2017. Across treatment sites, there was a wide variation in the utilisation of FOLFOXIRI and EGFRi therapy; bevacizumab use was more consistent. A clear impact on survival outcomes from these regimens is not evident, potentially due to multiple confounders. CONCLUSION: Doublet chemotherapy + bevacizumab remains the dominant initial strategy, with limited uptake of triplet chemotherapy and of EGFRi. Potential explanations include uncertainty about the significance of post hoc analyses for EGFRi and concerns regarding adverse events for both strategies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Productos Biológicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Australia/epidemiología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/uso terapéutico , Sistema de Registros , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Thirty-day mortality after chemotherapy has been suggested as a marker of quality in oncology care. Retrospective audits worldwide have put this figure at between 8.1% and 43%, with previous retrospective Australian audits putting this figure at between 3.4% and 18%. To date, there has not been a prospective cohort study of patients receiving palliative intent chemotherapy at an Australian chemotherapy day unit. AIM: The aim of the study is to benchmark 30-day mortality for patients receiving palliative intent chemotherapy and identify associated factors at an Australian tertiary cancer centre. METHODS AND RESULTS: A prospective cohort study of all patients with a diagnosis of malignancy referred for palliative intent intravenous chemotherapy to the Sunshine Hospital Chemotherapy Day Unit over a 12-month period. The primary outcome was death within 30 days of receiving palliative intent chemotherapy. Other outcome measures included place of death and whether the patient received an outpatient palliative care referral. A total of 314 patients were enrolled in the study, and 98 patients died within the audit period. Of these, 21 (6.6%) died within 30 days of commencing palliative intent chemotherapy, and 60 (18.8%) died more than 30 days after receiving chemotherapy. Of the 34 patients that were referred, but did not start chemotherapy, 18 (52%) died. Multivariable logistic regression found that patients who received an outpatient palliative care referral and received chemotherapy were more likely to die within 30 days, although these did not reach statistical significance. CONCLUSION(S): This prospective cohort study demonstrated that 6.6% of patients died within 30 days of the administration of palliative intent chemotherapy; however, none of the prespecified factors were found to be statistically significantly associated with 30-day mortality.
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Antineoplásicos/uso terapéutico , Neoplasias/mortalidad , Cuidados Paliativos , Anciano , Atención Ambulatoria , Australia , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Estudios Prospectivos , Centros de Atención Terciaria , Factores de TiempoRESUMEN
AIM: Precision oncology involves molecularly matching patients to targeted agents usually in early drug development (EDD) programs. Molecular profiling (MP) identifies actionable targets. Comprehensive commercial MP platforms are costly and in resource limited environments, a more practical approach to MP is necessary to support EDD and precision oncology. We adopted a clinician-directed, tailored approach to MP to enrol patients onto molecularly targeted trials. We report the feasibility of this approach. METHODS: All patients referred to the Royal Melbourne Hospital (RMH) EDD between September 2013 and September 2015 were identified in a prospective database. Key captured data included clinicopathological data, MP platform ordered (if any), molecular targets identified and subsequent enrolment onto clinical trials. EDD-clinician decisions to order MP and the platform utilized was guided by patient consultation, tumor type, trial availability and requirement for molecular information. RESULTS: We identified 377 patients referred to RMH EDD. A total of 216 (57%) had MP ordered. The remainder had known actionable targets (19%), or were inappropriate for clinical trials (24%). In those undergoing MP, 187 genetic aberrations were found in 113 patients with 98 considered actionable targets in 86 patients. Ninety-eight (25%) patients were enrolled onto a clinical trial, including 40 (11%) receiving molecularly matched treatments. Median progression-free survival was improved in patients enrolled onto molecularly matched trials compared to those on unmatched trials (3.6 months vs 1.9 months, HR 0.58 [0.38-0.89], P = 0.013). CONCLUSION: A clinician-directed, tailored approach to the use of MP is feasible, resulting in 11% of patients enrolled onto molecularly matched trials.
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Neoplasias/tratamiento farmacológico , Neoplasias/genética , Medicina de Precisión/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Estudios ProspectivosRESUMEN
AIM: Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC. METHODS: Nineteen medical oncologists from nine hospitals contributing data to TRACC completed a 34-question survey regarding their impression of the management and outcomes of mCRC at their own practice and other hospitals contributing to the database. Responses were then compared with TRACC data to determine how closely their impressions reflected actual practice. RESULTS: Data on 1300 patients with mCRC were available. Median clinician estimated frequency of KRAS testing within 6 months of diagnosis was 80% (range: 20-100%); the TRACC documented rate was 43%. Clinicians generally overestimated the rates of first-line treatment, particularly in patients over 75 years. Estimate for bevacizumab in first line was 60% (35-80%) versus 49% in TRACC. Estimated rate for liver resection varied substantially (5-35%), and the estimated median (27%) was inconsistent with the TRACC rate (12%). Oncologists generally felt their practice was similar to other hospitals. CONCLUSIONS: Oncologists' estimates of current clinical practice varied and were discordant with the TRACC database, often with a tendency to overestimate interventions. Clinician surveys alone do not reliably capture contemporary clinical practices in mCRC.
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Neoplasias Colorrectales/terapia , Oncólogos/normas , Adulto , Anciano , Australia , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
LESSONS LEARNED: Trebananib leveraging anti-angiogenic mechanism that is distinct from the classic sorafenib anti-vascular endothelial growth factor inhibition did not demonstrate improved progression-free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang-2 levels' association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang-2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang-2. BACKGROUND: Ang-1 and Ang-2 are angiopoietins thought to promote neovascularization via activation of the Tie-2 angiopoietin receptor. Trebananib sequesters Ang-1 and Ang-2, preventing interaction with the Tie-2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang-2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC). METHODS: Patients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs-Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression-free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang-2. RESULTS: Thirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar-plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One death was due to hepatic failure. Serum Ang-2 dichotomized at the median was associated with improved OS in both cohorts. CONCLUSION: There was no improvement in PFS rate at 4 months in either cohort, when compared with sorafenib historical control.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Angiopoyetina 2/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Hepatocelular/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Sorafenib , Resultado del TratamientoRESUMEN
PURPOSE: We evaluated the activity of regorafenib, an oral multikinase inhibitor, in advanced gastric adenocarcinoma. PATIENTS AND METHODS: We conducted an international (Australia and New Zealand, South Korea, and Canada) randomized phase II trial in which patients were randomly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease (one v two) and region. Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred. The primary end point was progression-free survival (PFS). Final analysis included data to December 31, 2014. RESULTS: A total of 152 patients were randomly assigned from November 7, 2012, to February 25, 2014, yielding 147 evaluable patients (regorafenib, n = 97; placebo, n = 50). Baseline characteristics were balanced. Median PFS significantly differed between groups (regorafenib, 2.6 months; 95% CI, 1.8 to 3.1 and placebo, 0.9 months; 95% CI, 0.9 to 0.9; hazard ratio [HR], 0.40; 95% CI, 0.28 to 0.59; P < .001). The effect was greater in South Korea than in Australia, New Zealand, and Canada combined (HR, 0.12 v 0.61; interaction P < .001) but consistent across age, neutrophil-to-lymphocyte ratio, primary site, lines of chemotherapy, peritoneal metastasis presence, number of metastatic sites, and plasma vascular endothelial growth factor A. A survival trend in favor of regorafenib was seen (median, 5.8 months; 95% CI, 4.4 to 6.8 v 4.5 months; 95% CI, 3.4 to 5.2; HR, 0.74; P = .147). Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression. Regorafenib toxicity was similar to that previously reported. CONCLUSION: In this phase II trial, regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma. Regional differences were found, but regorafenib was effective in both regional groups. A phase III trial is planned.