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BACKGROUND: PLAnning Treatment For Oesophago-gastric Cancer: a Randomised Maintenance Therapy Trial (PLATFORM) is an adaptive phase II study assessing the role of maintenance therapies in advanced oesophago-gastric (OG) adenocarcinoma. We evaluated the role of the anti-programmed death-ligand 1 (PD-L1) inhibitor durvalumab in these patients. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2-negative locally advanced or metastatic OG adenocarcinoma with disease control or response to 18 weeks of platinum-based first-line chemotherapy were randomised to active surveillance or maintenance durvalumab. The primary endpoint was progression-free survival (PFS). Safety was assessed in all patients who had commenced surveillance visits or received at least one dose of durvalumab. Exploratory survival analyses according to PD-L1 Combined Positive Score (CPS) and immune (biomarker-positive) or angiogenesis dominant (biomarker-negative) tumour microenvironment (TME) phenotypes were conducted. RESULTS: Between March 2015 and April 2020, 205 patients were randomised to surveillance (n = 100) and durvalumab (n = 105). No significant differences were seen in PFS [hazard ratio (HR) 0.84, P = 0.13] and overall survival (OS; HR 0.98, P = 0.45) between surveillance and durvalumab. Five patients randomised to durvalumab demonstrated incremental radiological responses compared with none with surveillance. Treatment-related adverse events occurred in 77 (76.2%) durvalumab-assigned patients. A favourable effect in OS with durvalumab over surveillance in CPS ≥5 and immune biomarker-positive patients was observed compared with CPS <5 and biomarker-negative subgroups, respectively: CPS ≥5 versus <5: HR 0.63, 95% confidence interval (CI) 0.32-1.22 versus HR 0.93, 95% CI 0.44-1.96; biomarker-positive versus negative: HR 0.60, 95% CI 0.29-1.23 versus HR 0.84, 95% CI 0.42-1.65. CONCLUSION: Maintenance durvalumab does not improve PFS in patients with OG adenocarcinoma who respond to first-line chemotherapy but induced incremental radiological responses in a subset of patients. TME characterisation could refine patient selection for anti-PD-L1 therapy above PD-L1 CPS alone.
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Adenocarcinoma , Anticuerpos Monoclonales , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Adenocarcinoma/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Receptor ErbB-2/metabolismo , Anciano de 80 o más Años , Supervivencia sin ProgresiónRESUMEN
The clinical landscape for endometrial cancer in the UK is evolving to include new management guidelines and targeted treatment options. An understanding of current treatment and management practices in the UK will help services plan and adapt to upcoming changes. AIM: The purpose of this survey was to understand current and anticipated real-world practices for endometrial cancer care in the UK and potential areas for optimisation. MATERIALS AND METHODS: Telephone interviews were conducted in November/December 2021 with UK-based healthcare professionals involved in endometrial cancer management. Questions were aligned with the British Gynaecological Cancer Society/European Society for Medical Oncology recommendations, covering the pathway from diagnosis and treatment to follow-up. RESULTS: A total of 63 healthcare professionals (HCPs) involved in the management of patients with endometrial cancer participated in telephone interviews. The results highlighted variations in management and treatment practices for endometrial cancer and suggest that current UK practice appears to diverge from national and international guidance in some instances. While somatic mismatch repair deficiency testing was used by 89.7% of respondents as mainstream testing, the survey highlighted a lack of access to other key molecular biomarker tests, such as polymerase epsilon (POLE) sequencing (used by only 9.8% of HCPs at the time of the survey). CONCLUSION: The results highlighted several perceived practical barriers to the swift adoption of new therapeutic options, including funding access, limited staff, treatment-related resources, staff education, and support. Our findings support the need for better access to biomarkers that could enable more effective and targeted treatments.
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BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.
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Neoplasias Ováricas , Humanos , Femenino , Carboplatino , Trabectedina , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/etiología , Platino (Metal)/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/etiología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Doxorrubicina , Polietilenglicoles , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
PURPOSE: To evaluate prognostic value of integrated 2-deoxy-2-[F-18]fluoro-D: -glucose-positron emission tomography/computed tomography (FDG-PET/CT) and correlate histopathological subtype with maximum standardized uptake value (SUV(max)) and survival in patients with malignant mesothelioma (MM). PROCEDURES: Retrospective review of FDG-PET/CT scans, with derivation of SUV(max) of FDG-avid lesions, was performed in patients with biopsy-proven MM. Clinical follow-up and Kaplan-Meier survival analysis was performed. RESULTS: Forty-six patients (37 M:9 F; mean age 61 years) with MM had a FDG-PET/CT scan in a 30-month period. Follow-up was available on 44/46 (96%) patients. Metastatic disease was detected in 9/46 (20%) patients on FDG-PET/CT, where 8/9 were previously undetected. Better survival was found in patients without metastases (p value < 0.05). Mean SUV(max) of primary pleural lesions in patients with metastatic disease was significantly higher than in patients without metastatic disease (p value < 0.05). Progression-free survival was significantly better in the epithelioid histology group compared to the biphasic group (p value 0.015). CONCLUSIONS: Detection of extrathoracic metastases on FDG-PET/CT and nonepithelioid histopathology are poor prognostic indicators in patients with MM.
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Fluorodesoxiglucosa F18 , Mesotelioma/patología , Neoplasias Pleurales/patología , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada de Emisión/métodos , Adulto , Anciano , Anciano de 80 o más Años , Australia , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18/metabolismo , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Mesotelioma/diagnóstico por imagen , Persona de Mediana Edad , Neoplasias Pleurales/diagnóstico por imagen , Pronóstico , Radiografía , Radiofármacos/metabolismo , Factores de TiempoAsunto(s)
Adenocarcinoma/sangre , Antígeno Carcinoembrionario/análisis , Carcinoma Medular/sangre , Neoplasias del Ciego/sangre , Neoplasias Primarias Secundarias/sangre , Tomografía de Emisión de Positrones , Neoplasias de la Tiroides/sangre , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Carcinoma Medular/diagnóstico por imagen , Carcinoma Medular/cirugía , Neoplasias del Ciego/tratamiento farmacológico , Neoplasias del Ciego/cirugía , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
Positron-emission tomography-computed tomography (PET/CT) is rapidly being integrated into the imaging pathways of several different tumour types, most frequently using the glucose analogue 2- [(18)F]-fluoro-2-deoxy-D-glucose (FDG). Integrated FDG-PET/CT combines functional and anatomical imaging to improve sensitivity and specificity of tumour detection. The aim of this article is to review the established, emerging, and future roles of FDG-PET/CT in the management of patients with colorectal cancer (CRC).
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Neoplasias Colorrectales/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Colonoscopía , Neoplasias Colorrectales/tratamiento farmacológico , Análisis Costo-Beneficio , Fluorodesoxiglucosa F18 , Humanos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estadificación de Neoplasias , Neoplasia Residual , Tomografía de Emisión de Positrones/economía , Tomografía de Emisión de Positrones/tendencias , Radiofármacos , Planificación de la Radioterapia Asistida por Computador , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/economía , Tomografía Computarizada por Rayos X/tendencias , Reino UnidoRESUMEN
This retrospective study looks at the differences between adolescents (15-19 years) and young adults (20-25 years), diagnosed with Hodgkin lymphoma and treated at the same adult institution. Outcome according to risk category was evaluated, and although there were no significant differences in the whole cohort, or low and intermediate-risk categories, high-risk adolescent patients had a significantly worse outcome compared to that of young adults. In these high-risk patients, 5-year event free survival was 43.6% in adolescents compared to 58.7% in young adults (log-rank survival p=0.03), and the 5-year overall survival in adolescents was 66.7% compared to 84.4% in the young adults (p=0.04). Possible contributing factors to this inferior outcome in these high-risk patients were explored. The difference could not be explained in terms of differences in histological subtype (p=0.5), proportion of patients with bulky (p=0.6) or extranodal disease (p=0.6), initial treatment received (chemotherapy alone compared to combination therapy, p=0.2), or proportion proceeding to high-dose treatment after initial treatment failure (p=0.6). There was no difference in the documented number of delays, dose reductions or episodes of non-compliance during initial treatment in the two high-risk age groups. A significantly greater proportion of high-risk adolescents had primary progressive disease (PPD) [eight high-risk adolescents (33.3%) compared to two high-risk young adults (7.7%), p=0.02].
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Enfermedad de Hodgkin/mortalidad , Adolescente , Adulto , Factores de Edad , Enfermedad de Hodgkin/terapia , Humanos , Estudios Retrospectivos , RiesgoRESUMEN
The therapeutic options and subsequent survival of colorectal cancer (CRC) patients has increased substantially over recent years. While surgical excision of the primary cancer results in cure of approximately 50% of patients, recurrence and metastatic disease still remains a significant cause of death. Although resection of liver or lung metastases can result in cure, relapse rates remain high, indicating that patient selection needs improvement. Positron emission tomography (PET) technology has a great deal to offer with respect to CRC management, particularly in the setting of patient selection for metastasectomy and in the evaluation of possible recurrent disease, however it has not yet become a routine part of the management of all CRC patients. This review article aims to discuss the current and future implications of PET technology in the optimal management of CRC patients throughout their care pathway.
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Neoplasias Colorrectales/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía de Emisión de Positrones/tendencias , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Predicción , Humanos , Inmunohistoquímica , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Tomografía de Emisión de Positrones/normas , Pronóstico , Factores de Riesgo , Rol , Sensibilidad y Especificidad , Análisis de SupervivenciaRESUMEN
With the development of an integrated treatment approach, the cure rate and survival of patients with Hodgkin Lymphoma (HL) is now high. Treatment tailored to stage, using chemotherapy, with or without involved field radiotherapy is the standard of care. Paediatric oncologists have been developing treatment regimens to maximise cure rate whilst trying to minimise the associated late side-effects, and cure rates in children are now often greater than 90%. It has been suggested that the outcome of adolescents with HL does not match that of younger children, but published data focusing on this group of patients is scarce. Future treatment strategies may direct the treatment of adolescents with HL away from the current "adult" regimens, and closer to that currently received by children, but prospective randomised trials are required. Rationalisation of both chemotherapy and radiotherapy administered to children and adolescents aims to minimise the risk of significant long-term side effects without sacrificing high cure rates. Infertility, secondary malignancies, cardiac and respiratory morbidity are all significant risks of current combined modality treatment that need to be discussed when obtaining informed consent and may influence the choice of treatment offered or accepted. Monitoring late effects of treatment (both physical and psychological) is especially important in this group of young patients.
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Enfermedad de Hodgkin , Adolescente , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/fisiopatología , Enfermedad de Hodgkin/psicología , Humanos , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Recurrencia , Medición de RiesgoRESUMEN
In this study, a beta-adrenergic blocker in combination with digoxin provided marginal protection against atrial fibrillation/flutter after coronary artery surgery. The economic comparison of patients who did and did not develop atrial fibrillation/flutter indicates that prevention of these arrhythmias can have a significant impact on length of hospital stay and cost of this common surgical procedure.
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Acebutolol/uso terapéutico , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/prevención & control , Aleteo Atrial/prevención & control , Puente de Arteria Coronaria/efectos adversos , Digoxina/uso terapéutico , Anciano , Fibrilación Atrial/etiología , Aleteo Atrial/etiología , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Factores de Tiempo , Resultado del TratamientoRESUMEN
Prostaglandin E2 (PGE2) was given to 60 patients to induce labor at term. Two dosage schedules were used: 30 patients were given 0.5 mg hourly and 30 patients were given 1.0 mg hourly. Membranes were ruptured when active labor had occurred. The Bishop score was used for inducibility quotient. In general, the higher the Bishop score, the shorter the delivery time. The 1.0 mg dosage schedule decreased the induction time in both nulliparas and multiparas. There were 55 vaginal deliveries. Five patients were delivered by cesarean section for obstetrical indications; two were in active labor. The overall success rate was 91.6%. No fetal distress occurred that could be attributed to the PGE2. Maternal complications consisted of nausea and vomiting.