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OBJECTIVE: To date, there are no predictive biomarkers to guide selection of patients with gastric cancer (GC) who benefit from paclitaxel. Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) was a 2×2 factorial randomised phase III study in which patients with GC were randomised to Pac-S-1 (paclitaxel +S-1), Pac-UFT (paclitaxel +UFT), S-1 alone or UFT alone after curative surgery. DESIGN: The primary objective of this study was to identify a gene signature that predicts survival benefit from paclitaxel chemotherapy in GC patients. SAMIT GC samples were profiled using a customised 476 gene NanoString panel. A random forest machine-learning model was applied on the NanoString profiles to develop a gene signature. An independent cohort of metastatic patients with GC treated with paclitaxel and ramucirumab (Pac-Ram) served as an external validation cohort. RESULTS: From the SAMIT trial 499 samples were analysed in this study. From the Pac-S-1 training cohort, the random forest model generated a 19-gene signature assigning patients to two groups: Pac-Sensitive and Pac-Resistant. In the Pac-UFT validation cohort, Pac-Sensitive patients exhibited a significant improvement in disease free survival (DFS): 3-year DFS 66% vs 40% (HR 0.44, p=0.0029). There was no survival difference between Pac-Sensitive and Pac-Resistant in the UFT or S-1 alone arms, test of interaction p<0.001. In the external Pac-Ram validation cohort, the signature predicted benefit for Pac-Sensitive (median PFS 147 days vs 112 days, HR 0.48, p=0.022). CONCLUSION: Using machine-learning techniques on one of the largest GC trials (SAMIT), we identify a gene signature representing the first predictive biomarker for paclitaxel benefit. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry: C000000082 (SAMIT); ClinicalTrials.gov identifier, 02628951 (South Korean trial).
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Humanos , Aprendizado de Máquina , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVE: Patient involvement in treatment decisions is recommended in clinician-patient encounters. Little is known about how oncologists engage patients in shared decision making in non-Western countries. We assessed the prevalence of shared decision making among Singaporean oncologists and analysed how they discussed prognosis. METHODS: We audio-recorded 100 consultations between advanced cancer patients and their oncologists. We developed a coding system to assess oncologist encouragement of patient participation in decision making and disclosure of an explicit prognosis. We assessed patient and oncologist characteristics that predicted these behaviours. RESULTS: Forty-one consultations involved treatment discussions. Oncologists almost always listed more than one treatment option (90%). They also checked patient understanding (34%), discussed pros and cons (34%) and addressed uncertainty (29%). Oncologists discussed prognosis mostly qualitatively (34%) rather than explicitly (17%). They were more likely to give an explicit prognosis when patients/caregivers asked questions related to prognosis. CONCLUSION: Oncologists in our sample engaged their patients in decision making. They have areas in which they can improve to involve patients at a deeper level to ensure shared decision making. Findings will be used to develop an intervention targeting oncologists and patients to promote patient involvement in decision making.
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Cuidadores/estatística & dados numéricos , Tomada de Decisão Compartilhada , Neoplasias/terapia , Oncologistas/estatística & dados numéricos , Pacientes/estatística & dados numéricos , Encaminhamento e Consulta , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Prognóstico , Singapura , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Early diagnosis of metastatic epidural spinal cord compression (MESCC) is vital to expedite therapy and prevent paralysis. Staging CT is performed routinely in cancer patients and presents an opportunity for earlier diagnosis. METHODS: This retrospective study included 123 CT scans from 101 patients who underwent spine MRI within 30 days, excluding 549 CT scans from 216 patients due to CT performed post-MRI, non-contrast CT, or a gap greater than 30 days between modalities. Reference standard MESCC gradings on CT were provided in consensus via two spine radiologists (11 and 7 years of experience) analyzing the MRI scans. CT scans were labeled using the original reports and by three radiologists (3, 13, and 14 years of experience) using dedicated CT windowing. RESULTS: For normal/none versus low/high-grade MESCC per CT scan, all radiologists demonstrated almost perfect agreement with kappa values ranging from 0.866 (95% CI 0.787-0.945) to 0.947 (95% CI 0.899-0.995), compared to slight agreement for the reports (kappa = 0.095, 95%CI -0.098-0.287). Radiologists also showed high sensitivities ranging from 91.51 (95% CI 84.49-96.04) to 98.11 (95% CI 93.35-99.77), compared to 44.34 (95% CI 34.69-54.31) for the reports. CONCLUSION: Dedicated radiologist review for MESCC on CT showed high interobserver agreement and sensitivity compared to the current standard of care.
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Background: Metastatic epidural spinal cord compression (MESCC) is a disastrous complication of advanced malignancy. Deep learning (DL) models for automatic MESCC classification on staging CT were developed to aid earlier diagnosis. Methods: This retrospective study included 444 CT staging studies from 185 patients with suspected MESCC who underwent MRI spine studies within 60 days of the CT studies. The DL model training/validation dataset consisted of 316/358 (88%) and the test set of 42/358 (12%) CT studies. Training/validation and test datasets were labeled in consensus by two subspecialized radiologists (6 and 11-years-experience) using the MRI studies as the reference standard. Test sets were labeled by the developed DL models and four radiologists (2−7 years of experience) for comparison. Results: DL models showed almost-perfect interobserver agreement for classification of CT spine images into normal, low, and high-grade MESCC, with kappas ranging from 0.873−0.911 (p < 0.001). The DL models (lowest κ = 0.873, 95% CI 0.858−0.887) also showed superior interobserver agreement compared to two of the four radiologists for three-class classification, including a specialist (κ = 0.820, 95% CI 0.803−0.837) and general radiologist (κ = 0.726, 95% CI 0.706−0.747), both p < 0.001. Conclusion: DL models for the MESCC classification on a CT showed comparable to superior interobserver agreement to radiologists and could be used to aid earlier diagnosis.