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1.
Clin Case Rep ; 12(6): e8929, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38799519

RESUMEN

Serum carbohydrate antigen 19-9 (CA19-9) is used for recurrence surveillance in patients with resected pancreatic ductal adenocarcinoma (PDAC). This report describes the association of increasing CA19-9 in a male PDAC survivor with presence of prostatic hyperplasia. Unexplained elevation of CA19-9 in male PDAC survivors might be attributable to benign prostatic conditions.

2.
J Thorac Oncol ; 19(4): 650-652, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38340108

RESUMEN

Adjuvant osimertinib represents a recent paradigm shift in the management of resected EGFR-mutated lung cancer. The optimal subsequent treatment of patients who relapse after completion of 3 years of adjuvant osimertinib is unknown. Here, we report two cases of complete response to osimertinib rechallenge after relapse from previous adjuvant osimertinib use, and a serial molecular panel exhibiting a lack of acquired resistance mechanisms. Future prospective studies are warranted to confirm the optimal treatment of patients who relapse after previous adjuvant osimertinib.


Asunto(s)
Acrilamidas , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Recurrencia , Mutación , Inhibidores de Proteínas Quinasas
3.
Int J Pharm ; 651: 123790, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38190951

RESUMEN

Adjuvant chemotherapy is highly recommended for liver cancer to enhance survival rates due to its tendency to recur frequently. Localized drug-eluting implants have gained traction as an alternative to overcome the limitations of systemic chemotherapy. This work describes the development of biodegradable 3D printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) with different infill percentages where the 5FU layers were 40%, 30%, and 30% and Cis layers were 10%, 15%, and 10% for films A, B, and C, respectively. The relevant characterization tests were performed, and the drug content of films was 0.68, 0.50, and 0.50 mg of 5FU and 0.39, 0.80, and 0.34 mg of Cis for films A, B, and C, respectively. Cis release was affected by the alterations to the film design, where films A, B, and C showed complete release at 12, 14, and 23 days, respectively. However, 5FU was released over 24 h for all films. The films were stable for up to two weeks after storage at 25 °C/65% relative humidity and four weeks at 4 °C where drug content, tensile strength, FTIR, and thermal analysis results demonstrated negligible alterations. The cytotoxicity of the films was assessed by MTS assays using HepG2 cell lines demonstrating up to 81% reduction in cell viability compared to blank films. Moreover, apoptosis was confirmed by Western Blots and the determination of mitochondrial cell potential, highlighting the potential of these films as a promising approach in adjuvant chemotherapy.


Asunto(s)
Sistemas de Liberación de Medicamentos , Neoplasias Hepáticas , Humanos , Sistemas de Liberación de Medicamentos/métodos , Fluorouracilo , Neoplasias Hepáticas/tratamiento farmacológico , Apoptosis , Cisplatino , Impresión Tridimensional
4.
Cancer Med ; 12(1): 368-378, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35603739

RESUMEN

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is an ultra-rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting. METHODS: We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 22 patients with MCS between 2001-2022. Median age was 28 (range 10-59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow-up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow-up of 50.9  (range 0.4-210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8-182.3). There was improved OS for patients with localised disease who had surgical resection of the primary (p = 0.003) and those with ECOG 0-1 compared to 2-3 (p = 0.023) on univariate analysis. CONCLUSIONS: This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies.


Asunto(s)
Neoplasias Óseas , Condrosarcoma Mesenquimal , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Condrosarcoma Mesenquimal/cirugía , Neoplasias Óseas/patología , Australia/epidemiología , Estudios de Cohortes , Estudios Retrospectivos
6.
BMJ Open ; 12(8): e060907, 2022 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-36038161

RESUMEN

INTRODUCTION: Lung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand. METHODS AND ANALYSIS: Patient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight. ETHICS AND DISSEMINATION: The ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Australia/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/terapia , Nueva Zelanda/epidemiología , Sistema de Registros
7.
Pancreas ; 51(5): 490-495, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35849065

RESUMEN

OBJECTIVES: Nab-paclitaxel has radiosensitizing antitumor efficacy in pancreatic cancer. We aimed to establish maximum tolerated dose (MTD) of nab-paclitaxel with radiotherapy in unresectable locally advanced pancreatic cancer. METHODS: In a phase I dose escalation trial patients received weekly nab-paclitaxel for 6 weeks with external beam radiotherapy (EBRT). 3 + 3 design was used with nab-paclitaxel doses: 25 mg/m 2 (cohort 1), 50 mg/m 2 (cohort 2), 75 mg/m 2 (cohort 3), and 100 mg/m 2 (cohort 4). Primary endpoint was MTD. Secondary objectives were progression-free survival and overall survival. RESULTS: Fourteen patients were recruited. Median age was 69 years (range, 40-86). Grade 1/2 toxicities were nausea (93%), vomiting (54%), diarrhea (57%), and fatigue (69%). There were no dose limiting toxicities (DLT) in cohorts 1 to 3. In cohort 4, DLTs of febrile neutropenia and enterocolitis were observed in patient 1. Subsequent DLT of febrile neutropenia and enterocolitis occurred in patient 5 in the expanded cohort. Following chemoradiotherapy median progression-free survival was 4.7 months (95% confidence interval, 2.5-27.5) and median overall survival was 10.8 months (95% confidence interval, 6.37-25.2). CONCLUSIONS: Nab-paclitaxel and EBRT was well-tolerated at doses below 100 mg/m 2 . The MTD and recommended phase II study dose for nab-paclitaxel with EBRT is 75 mg/m 2 in this disease.


Asunto(s)
Adenocarcinoma , Albúminas , Quimioradioterapia , Paclitaxel , Neoplasias Pancreáticas , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Albúminas/toxicidad , Quimioradioterapia/efectos adversos , Enterocolitis/inducido químicamente , Neutropenia Febril/inducido químicamente , Humanos , Persona de Mediana Edad , Paclitaxel/toxicidad , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas
8.
Asia Pac J Clin Oncol ; 18(6): 605-613, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35098667

RESUMEN

AIM: Despite lack of advances in the first-line systemic therapy, the overall survival (OS) has continued to improve in patients with advanced soft tissue sarcoma (STS) with the recent estimation of median OS at 20 months. Several systemic therapy options are available now for the second-line and beyond, with more treatment tailored to histology and molecular subtype. The aim of this retrospective study was to characterize current patterns of care in managing patients with advanced STS (aSTS) in Australia. METHODS: Sarcoma databases from 7 Australian sarcoma services were accessed to identify patients diagnosed with locally advanced inoperable and/or metastatic STS between January 1, 2010 and December 31, 2015. Baseline clinicopathological factors and initial treatment patterns were descriptively analyzed. For the Victorian cohort where treatment of aSTS and follow-up details were available, further exploratory analysis was conducted to determine the impact of patient and tumor characteristics and the use of palliative-intent treatment OS. RESULTS: Of 2261 cases of STS, 671 were deemed as aSTS. Two thirds were relapsed disease with a mean 1.9 years from initial diagnosis. Median age at diagnosis of aSTS was 59 years (18-95 years) and 56.3% was male. Histology classification revealed four main subtypes: undifferentiated pleomorphic sarcoma (UPS) (23.1%), leiomyosarcoma (18.2%), liposarcoma (12.8%), synovial sarcoma (8.2%), and other comprising 14 STS subtypes. For the Victorian cohort (N = 361), approximately 80% of patients accessed palliative-intent treatment of various modalities. Nearly 40% of patients underwent tumor-debulking surgery or metastasectomy, of which lung wedge resection was the most common (N = 83, 47.7%). A total of 438 palliative-intent radiotherapy treatments were delivered to 259 patients (71.7%), with the majority in the form of external beam radiotherapy. Palliative-intent systemic therapy was delivered to 51.5% of patients (N = 186), mostly (73%). Anthracycline-based therapy was the most commonly delivered therapy (N = 135, 72.6%). Approximately half of the patients in each line of therapy failed to proceed to the subsequent line of systemic therapy with 29.4% receiving three or more lines of therapy (N = 55). A total of 18.3% of patient (N = 34) participated in clinical trials or accessed off-label drugs. The median OS for the Victoria cohort was 15.4 months (95% confidence interval: 12.1, 18.2). The UPS histology subtype was associated with poorer OS, whereas receiving any modality of palliative-intent treatment conferred survival benefit. CONCLUSION: In Australia, aSTS is managed with diverse treatment approaches comprising various therapy modalities. Further work is planned in describing healthcare resource utilization and estimating costs by this patient cohort.


Asunto(s)
Leiomiosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Masculino , Estudios Retrospectivos , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/terapia , Leiomiosarcoma/patología , Victoria/epidemiología
9.
Endoscopy ; 54(1): 75-80, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33440437

RESUMEN

BACKGROUND: This study evaluated clinical outcomes of combined chemotherapy and endoscopic ultrasound (EUS)-guided intratumoral radioactive phosphorus-32 (32P) implantation in locally advanced pancreatic adenocarcinoma (LAPC). METHODS: Consecutive patients with newly diagnosed LAPC were recruited over 20 months. Baseline computed tomography and 18F-2-fluoro-2-deoxy-D-glucose (18FDG) positron emission tomography-computed tomography were performed and repeated after 12 weeks to assess treatment response. Following two cycles of conventional chemotherapy, patients underwent EUS-guided 32P implantation followed by six chemotherapy cycles. RESULTS: 12 patients with LAPC (median age 69 years [interquartile range 61.5-73.3]; 8 male) completed treatment. Technical success was 100 % with no procedural complications. At 12 weeks, median reduction in tumor volume was 8.2 cm3 (95 % confidence interval 4.95-10.85; P = 0.003), with minimal or no 18FDG uptake in nine patients (75 %). Tumor downstaging was achieved in six patients (50 %), leading to successful resection in five (42 %), including four R0 resections (80 %). CONCLUSIONS: EUS-guided 32P implantation was feasible, well tolerated, and resulted in a 42 % surgical resection rate. Further evaluation in a larger randomized multicenter trial is warranted.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/terapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Masculino , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Radioisótopos de Fósforo , Proyectos Piloto , Ultrasonografía Intervencional
10.
ANZ J Surg ; 91(12): 2675-2682, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34617383

RESUMEN

BACKGROUND: A single state-wide upper gastrointestinal (GI) cancer video-linked multidisciplinary team (MDT) meeting guides management and evidence-based care for all newly diagnosed upper GI cancer patients in South Australia. This study determined the patterns of care and outcomes for patients diagnosed with gastric and gastro-oesophageal junction (GOJ) cancers. METHODS: Patients diagnosed with gastric cancer and GOJ (Siewert III) cancer between June 2012 and June 2016 were included. Patient demographics, cancer stage, histology, diagnostic modalities and treatment data was analysed from a prospective database. Stage-specific survival outcomes were determined and analysed for each treatment modality. RESULTS: The study included 218 patients and at diagnosis 132 (61%) patients had stage I-III and 86 (39%) patients had stage IV disease. One hundred and ninety-five (89%) patients had gastric cancer and 23 (11%) had GOJ cancer (Siewert III). One hundred and nine (50%) patients underwent surgery, with 92% R0 resection rate. Forty-six patients received perioperative chemotherapy and 111 (51%) patients received palliative intent treatment. Median overall survival for stage II, III and IV cancers was 57.6 (95% CI 57.6-NR), 22.8 (95% CI 20.4-43.2), and 6.0 months (95% CI 4.8-8.4) respectively (p < 0.001). Median overall survival for patients who underwent perioperative chemotherapy and surgery was not reached as compared to 44.4 months (95% CI 28.8-NR) for patients who underwent surgery alone. CONCLUSION: Treatment outcomes for patients with gastric and GOJ cancer managed across South Australia met contemporary evidence-based practice. However, as most patients continue to present with late-stage disease, longer-term survival remains poor.


Asunto(s)
Neoplasias Gástricas , Neoplasias Testiculares , Australia/epidemiología , Unión Esofagogástrica , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/terapia
11.
Expert Rev Anticancer Ther ; 21(2): 193-203, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33161803

RESUMEN

Introduction: A comprehensive trimodality approach has become the standard of care for patients with locally advanced rectal cancer. However, the sequencing and duration of chemotherapy and chemoradiotherapy around surgery varies between clinical studies and geographical regions. Growing evidence is also mounting for strategies such as total neoadjuvant therapy and non-operative management for carefully selected patients.Areas covered: We provide a perspective review of the current evidence and controversies in the treatment of locally advanced rectal cancer including the recent updates from the 2020 ASCO annual conference.Expert opinion: With ongoing advances in the management of locally advanced rectal cancer, a multidisciplinary team approach is necessary as treatments could involve multiple approaches. Chemoradiotherapy whether short or long course followed by at least 3 months of systemic chemotherapy may be the preferred option to balance local and distant disease control. Albeit the choice of doublet or triplet chemotherapy is still controversial. As total neoadjuvant treatment becomes part of the standard of care in rectal cancer, modification of the surveillance schedule is needed to detect early recurrences which may be limited by resources and availability of services.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioradioterapia/métodos , Neoplasias del Recto/terapia , Humanos , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia , Grupo de Atención al Paciente/organización & administración , Selección de Paciente , Neoplasias del Recto/patología , Resultado del Tratamiento
12.
J Cardiol Cases ; 22(2): 90-93, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32774528

RESUMEN

Cardiac angiosarcomas are a rare group of soft tissue sarcomas, characterized by aggressive local growth and early spread. Because this is an uncommon disease, there is currently no standard treatment approach. When localized, surgery appears to lead to the best outcomes, but this can be technically challenging and not always feasible. Upfront chemoradiotherapy provides an alternative that may shrink the tumor to enable definitive surgical resection. We report a case of primary cardiac angiosarcoma with a complete metabolic and pathological response after upfront chemoradiotherapy with paclitaxel, who then underwent surgery, as a potential treatment option for patients with this rare condition. .

14.
J Geriatr Oncol ; 11(1): 114-120, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31023599

RESUMEN

BACKGROUND: Treatment of older patients with myelodysplastic syndrome (MDS) is based on disease biology and performance status. Performance status, however, does not reflect increasing co-morbidities, functional dependence or psychosocial issues in older patients. PATIENTS AND METHODS: This prospective study evaluated the burden of geriatric related health issues, assessed feasibility of "tailored" Comprehensive Geriatric Assessment (CGA), and compared treatment duration and survival in older patients with MDS and oligoblastic acute myeloid leukemia with and without deficits in CGA domains (n = 98). RESULTS: Although only 27 (28%) patients had an Eastern Cooperative Oncology Group score ≥2, 78% (n = 77) patients had deficits in at least one CGA domain. Deficits were spread across all CGA domains, including dependence for instrumental activity of daily living (iADL; n = 33, 34%). Importantly, patients who were dependent for iADL (3.7 ±â€¯2.6 vs 12.1 ±â€¯7.9; p = .009), had cognitive impairment (3.5 ±â€¯2.1 vs. 10.9 ±â€¯7.9; p = .034) or impaired mobility (3.8 ±â€¯2.5 vs. 13.2 ±â€¯7.6; p = .001) completed significantly less azacitidine cycles as compared to those without these deficits. Cox-proportional regression showed that iADL dependency (hazard ratio 3.37; p = .008) and higher comorbidities (hazard ratio 4.7; p < .001) were associated with poor prognosis independent of disease related factors. Poor survival of iADL dependent patients was seen in both azacitidine (6 vs 19 months; p < .001) and supportive care cohorts (26 vs 48 months; p = .01). CONCLUSION: CGA detected geriatric related health issues, predicted poor survival and identified patients less likely to continue and benefit from azacitidine. Hence, CGA should be included in the treatment decision algorithm of older patients with MDS.


Asunto(s)
Evaluación Geriátrica , Síndromes Mielodisplásicos , Anciano , Azacitidina/uso terapéutico , Duración de la Terapia , Humanos , Síndromes Mielodisplásicos/tratamiento farmacológico , Estudios Prospectivos
15.
J Geriatr Oncol ; 11(6): 909-916, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31734077

RESUMEN

Early diagnosis of colorectal cancer (CRC) and access to optimal treatment achieves optimal cancer outcomes. However, CRC survival inequalities persist with a lower survival rate for older patients (≥65 years). Although the reasons for poorer cancer survival in older people are complex, evidence suggests that these patients are less likely to receive best practice care as indicated by access to multidisciplinary team (MDT) care. Three electronic databases were systematically searched to examine factors that affect access to, and clinical decision-making, in the context of MDT care of older people with CRC. We included studies reporting empirical data relating to predictors for a patient's case being discussed at a MDT meeting and/or factors that impact treatment decision-making during the meeting. From 303 returned titles and abstracts, eighteen articles were reviewed. Eight studies specifically selected older patients, with eligibility criteria varying from ≥65 to ≥80 years. Five articles explored predictors of MDT access, with all articles identifying age as a negative, and advanced stage as a positive predictor of MDT discussion. Fourteen studies explored factors that influenced the MDT decision-making process, with older age and presence of comorbid disease negatively influencing treatment decisions (cases less often discussed and/or treatment not recommended). A few studies identified access to a MDT discussion as an independent predictor for CRC treatment. Access to the MDT process for older patients with a CRC diagnosis should be based on relevant geriatric domains rather than on chronological age alone, which is expected to allow more appropriate clinical decision-making and reduce treatment inequities for older patients with cancer.


Asunto(s)
Toma de Decisiones Clínicas , Neoplasias del Colon/terapia , Neoplasias Colorrectales/terapia , Oncología Médica/organización & administración , Grupo de Atención al Paciente , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/diagnóstico , Neoplasias Colorrectales/diagnóstico , Toma de Decisiones , Humanos
16.
Leukemia ; 33(12): 2842-2853, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31089247

RESUMEN

Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational characteristics of T-MN (n = 129) and primary myelodysplastic syndrome (P-MDS, n = 108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct. TP53 mutations were more frequent in T-MN (29.5 vs. 7%), while spliceosomal complex mutations were more common in P-MDS (56.5 vs. 25.6%). In contrast to P-MDS, the ring sideroblasts (RS) phenotype was not associated with better survival in T-MN, most probably due to genetic association with TP53 mutations. SF3B1 was mutated in 96% of P-MDS with ≥15% RS, but in only 32% T-MN. TP53 mutations were detected in 92% T-MN with ≥15% RS and SF3B1 wild-type cases. Interestingly, T-MN and P-MDS patients with "Very low" or "Low" Revised International Prognostic Scoring System (IPSS-R) showed similar biological and clinical characteristics. In a Cox regression analysis, TP53 mutation was a poor prognostic factor in T-MN, independent of IPSS-R cytogenetics, disease-modifying therapy, and NRAS mutation. Our data have direct implications for T-MN management and provide evidence that, in addition to conventional disease parameters, mutational analysis should be incorporated in T-MN risk stratification.


Asunto(s)
Leucemia Mieloide/etiología , Mutación , Síndromes Mielodisplásicos/genética , Neoplasias Primarias Secundarias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Biomarcadores , Biopsia , Aberraciones Cromosómicas , Análisis Citogenético , Diagnóstico Diferencial , Femenino , Humanos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Tasa de Mutación , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/mortalidad , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/mortalidad , Pronóstico , Adulto Joven
17.
J Med Radiat Sci ; 66(1): 54-61, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30411540

RESUMEN

INTRODUCTION: The majority of pancreatic cancers present locally advanced and carry a high mortality rate. Treatment is challenging, with mixed data suggesting use of chemotherapy alone or in combination with radiotherapy. The use of radiotherapy has previously been limited due to lack of ability to deliver radiation to the tumour mass without causing significant toxicity to surrounding organs. Stereotactic body radiotherapy (SBRT) allows delivery of higher biologically equivalent dose in a shorter treatment duration. We sought to investigate the safety and application of this technique in our centre. METHOD: We enrolled 27 patients from 2015, identified as locally advanced unresectable with histologically confirmed, non-metastatic, pancreatic adenocarcinoma. All patients had endoscopically inserted fiducial markers and where possible concurrent chemotherapy was administered. Dose schedules ranged from 25 to 42 Gy in 5 or 3 fractions. RESULTS: With an overall median follow up of 9 months (range, 3-32.7), the median survival was 11.6 months. Of those alive at 1 year, the local control rate was 67%. Six patients had Grade 3 toxicity, and other six had Grade 2 toxicity. None had Grade 4 or above toxicity. The most common symptom recorded was fatigue. CONCLUSION: SBRT for locally advanced pancreatic cancer is technically complex but feasible in a high volume centre. SBRT is unique, allowing safe delivery of high radiation dose resulting in good local control and decreases treatment time making it an attractive option for patients with unresectable pancreatic cancer.


Asunto(s)
Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/radioterapia , Radiocirugia , Anciano , Anciano de 80 o más Años , Australia , Quimioradioterapia , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Radiocirugia/efectos adversos , Planificación de la Radioterapia Asistida por Computador , Seguridad
18.
Clin Cancer Res ; 24(16): 3838-3844, 2018 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-29739790

RESUMEN

Purpose: Inhibition of mTOR in addition to EGFR may overcome resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC). This phase Ib/II study evaluated the safety and efficacy of the combination of irinotecan, panitumumab, and everolimus.Patients and Methods: Patients with KRAS exon 2 wild-type (WT) mCRC following failure of fluoropyrimidine-based therapy received i.v. irinotecan and panitumumab every 2 weeks, and everolimus orally throughout a 14-day cycle. The primary endpoint of the phase II study was response rate (RR). Secondary survival outcomes were calculated using the Kaplan-Meier method, and results were analyzed as intention to treat. A preplanned exploratory biomarker analysis was performed.Results: Forty-nine patients were enrolled. Dose level 1 (irinotecan 200 mg/m2, panitumumab 6 mg/kg, and everolimus 5 mg alternate day) was declared the MTD with no dose-limiting toxicities in six patients. Forty patients were treated at dose level 1: median age, 60 years (37-76); 65% male; 45% and 52.5%, respectively, with Eastern Cooperative Oncology Group values of 0/1. Median dose intensity was 85%. Grade 3 toxicities were diarrhea (23%), mucositis (18%), rash (13%), fatigue (8%), dehydration (5%), neutropenia (20%), febrile neutropenia (8%), hypomagnesemia (20%), and hypokalemia (8%). Grade 4 toxicities were hypomagnesemia (5%) and neutropenia (3%). RR was 48%, and stable disease was 43%. Median progression-free survival (PFS) was 5.6 months, and median overall survival (OS) was 10.8 months. Twenty-five patients were RAS/RAF WT and had an RR of 60%, median PFS of 6.4 months, and OS of 11.8 months.Conclusions: The toxicity of the panitumumab, irinotecan, and everolimus regimen is as expected and manageable. The RR of 60% in all RAS/RAF WT supports further study of this combination. Clin Cancer Res; 24(16); 3838-44. ©2018 AACR.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Everolimus/administración & dosificación , Irinotecán/administración & dosificación , Panitumumab/administración & dosificación , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Supervivencia sin Progresión
19.
Asia Pac J Clin Oncol ; 14(1): 91-100, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28840978

RESUMEN

TITLE: Phase II study of celecoxib with docetaxel chemoradiotherapy (CRT) followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer. INTRODUCTION: Concurrent CRT has been associated with improvement in absolute 5-year survival by 10% and is the standard of care for inoperable stage III nonsmall cell lung cancer. Preclinical evidence suggests that cyclooxygenase-2 inhibition may increase the efficacy of CRT. METHODS: Patients were treated with CRT (weekly docetaxel at 30 mg/m2 over 6 weeks with concurrent external beam radiotherapy with 60 Gy in 30 fractions) followed by consolidation chemotherapy with docetaxel and cisplatin, each at 75 mg/m2 given 3 weekly for four cycles. Patients were to receive celecoxib 400 mg twice daily during treatment. Prophylactic cranial irradiation (30 Gy in 15 fractions) was offered if there was disease response. RESULTS: Twenty-four patients commenced CRT. Nineteen patients commenced consolidation therapy with 14 patients completing treatment. Twelve patients had treatment with celecoxib. In the total cohort, the median overall survival (mOS) was 21 months and progression-free survival (PFS) was 16 months. Overall response rate was 59% and disease control rate was 82%. Three patient deaths occurred. Significant grade 3/4 toxicity included radiation pneumonitis (17%), febrile neutropenia (17%), infection/sepsis with or with neutropenia (25%) and esophagitis (12.5%). Retrospective analysis of celecoxib versus no celecoxib treatment showed favorable mOS 26.5 versus 17.5 months and PFS 22 versus 16 months, but this did not reach statistical significance. CONCLUSIONS: The activity of this regimen has been demonstrated. Treatment-related toxicity was substantial. The role of celecoxib in addition to CRT could not be demonstrated in this study because of the small number of patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Celecoxib/administración & dosificación , Quimioradioterapia , Cisplatino/administración & dosificación , Quimioterapia de Consolidación , Irradiación Craneana , Supervivencia sin Enfermedad , Docetaxel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Taxoides/administración & dosificación
20.
J Eval Clin Pract ; 23(2): 361-368, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27554195

RESUMEN

Older people with cancer are at increased risk of falling. Falls risk-increasing drugs (FRIDs), comprising psychotropics and medications that cause orthostatic hypotension, are a potentially modifiable risk factor for falls. The objective of this study was to determine the prevalence and factors associated with use of FRIDs in older people with cancer. Patients aged ≥70 years who presented to a hospital outpatient clinic between January 2009 and July 2010 were included in the study. Information on current medication use, falls in previous 6 months, and frailty criteria was collected. Multinomial logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CIs) for factors associated with levels of FRID use. Overall, 76.1% (n = 293) of 383 patients used FRIDs. This comprised psychotropics (31.2%, n = 120) and medications causing orthostatic hypotension (69.9%, n = 269). In total, 24.0% (n = 92) patients reported falling in the previous 6 months. Risk factors for falling were associated with use of psychotropics but not orthostatic hypotension drugs. Patients with a history of falls had increased odds of using psychotropics (≥3 psychotropics; OR 13.50; 95%CI, 2.64-68.94). Likewise, frail patients had increased odds of using psychotropics (≥3 psychotropics; OR 27.78; 95%CI, 6.06-127.42). Risk factors for falling were associated with the use of psychotropics. This suggests that clinicians either do not recognize or underestimate the contribution of medications to falls in this high-risk patient group. Further efforts are needed to rationalize medication regimens at the time of patients' first presentation to outpatient oncology services.


Asunto(s)
Accidentes por Caídas/estadística & datos numéricos , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Instituciones Oncológicas/estadística & datos numéricos , Utilización de Medicamentos/estadística & datos numéricos , Psicotrópicos/efectos adversos , Anciano , Anciano de 80 o más Años , Australia , Estudios Transversales , Femenino , Humanos , Hipotensión Ortostática/inducido químicamente , Masculino , Oportunidad Relativa , Prevalencia , Factores de Riesgo
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