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PURPOSE: Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric measurements for prognostication at first tumour recurrence. METHODS: We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery. RESULTS: Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI [1.18, 5.57]; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI [0.95, 0.99]; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI [0.19, 0.98]; p = 0.04) were shown to have a better survival. CONCLUSION: Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis.
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Neoplasias Encefálicas , Glioma , Imagen por Resonancia Magnética , Recurrencia Local de Neoplasia , Humanos , Glioma/diagnóstico por imagen , Glioma/mortalidad , Glioma/cirugía , Glioma/patología , Masculino , Femenino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estudios Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Imagen por Resonancia Magnética/métodos , Adulto , Pronóstico , Anciano , Clasificación del Tumor , Carga Tumoral , Estimación de Kaplan-MeierRESUMEN
PURPOSE: Since few studies have investigated whether the Distress Thermometer (DT) in Asian adolescent and young adult (AYA) cancer patients (between 15 and 39 years), we investigated the appropriateness of the DT as a screening tool for psychological symptom burden in these AYA patients and to evaluate AYA patients' distress across a trajectory of three time points longitudinally over a 6-month period. METHODS: This was a prospective, longitudinal study. Recruited Asian AYA patients were diagnosed with lymphomas, sarcomas, primary brain malignancies, or germ cell tumors. Patients completed the DT, PedsQL Generic Core Scales, and the Rotterdam Symptom Checklist. Data were analyzed using STATA version 15. RESULTS: Approximately half of the patients experienced clinically significant DT distress (distress score ≥ 4) early in their cancer journey with 43.1% patients presenting with distress at time of diagnosis and 47.7% patients 1 month after diagnosis. Among AYA patients > 24 years old, worry (68.3%), insurance/financial issues (61%), treatment decisions (43.9%), work/school issues (41.5%), nervousness (41.5%), and sadness (41.5%) were the top five identified problems. On the other hand, the top five identified problems among AYA ≤ 24 years were worry (54.2%), nervousness (41.7%), bathing/dressing problems (37.5%), work/school issues (33.3%), and fatigue (33.3%). DT scores were significantly associated with certain psychological symptom burden items such as worry (p < 0.001), depressed mood (p = 0.020), and nervousness (p = 0.015). CONCLUSION: The DT is a useful screening tool for psychological distress in AYA cancer patients with clinically significant distress being identified in the early phases of the cancer journey.
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Neoplasias/psicología , Estrés Psicológico/psicología , Adolescente , Adulto , Pueblo Asiatico , Femenino , Humanos , Estudios Longitudinales , Masculino , Tamizaje Masivo , Estudios Prospectivos , Adulto JovenRESUMEN
INTRODUCTION: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We provide a review of a high-volume Asian institute's experience and survival outcomes with this procedure. METHODS: Data were prospectively collected from 201 consecutive CRS and HIPEC procedures performed in a single institution between April 2001 and November 2015. Our primary endpoints were overall survival (OS) and disease-free survival (DFS), and secondary endpoints were morbidity and mortality. RESULTS: 77% of patients were Chinese, 9% were Malay, 6% were Indian and 8% were other ethnicities. Primary tumours were colorectal (30%), ovarian (32%), appendiceal (20%), primary peritoneal (6.5%), mesothelioma (4.5%) and others (5%). The median peritoneal cancer index (PCI) was 12, and 92% of patients achieved a completeness of cytoreduction score (CC) of 0. High-grade morbidity occurred in 25.8% of cases, and there were no 30-day mortalities. At 5-years, the OS was 55.1% and DFS was 20.3%. Factors associated with improved OS on multivariate analysis were PCI <15 (p < 0.001) and a CC 0 (p = 0.016). CONCLUSIONS: The combined treatment of CRS and HIPEC is beneficial and is associated with reasonable morbidity and mortality in Asian patients with PC from colorectal, ovarian, appendiceal, primary peritoneal and mesothelioma primaries. Complete cytoreduction and extent of disease are the most important prognostic factors for survival.
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INTRODUCTION: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with or without early post-operative intraperitoneal chemotherapy (EPIC). We compared the morbidities, overall survival (OS) and disease free survival (DFS) between two groups of patients who underwent CRS and HIPEC alone and with EPIC at our institution. METHODS: A retrospective review of 111 patients with PC who were treated with CRS + HIPEC or CRS + HIPEC + EPIC in a single institution between January 2008 and April 2014 was performed. EPIC with 5-fluorouracil or paclitaxel was utilised, depending on the primary tumour. RESULTS: Patients who received EPIC had a higher proportion of grade III and above post- operative complications (58% versus 25%; p = 0.048) and a longer duration of hospitalisation (16 days versus 13 days; p = 0.019) than patients without EPIC. There were no significant OS and DFS differences between the EPIC and no EPIC groups (log-rank p = 0.231 and p = 0.144, respectively). CONCLUSION: The use of EPIC after CRS + HIPEC for PC potentially results in increased morbidity and longer hospitalisation, and is unlikely to affect survival outcomes. Based on our experience, EPIC is not recommended after CRS and HIPEC.
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Antineoplásicos/administración & dosificación , Quimioterapia del Cáncer por Perfusión Regional , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Neoplasias Peritoneales/terapia , Adolescente , Adulto , Anciano , Antineoplásicos/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Adulto JovenRESUMEN
BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in selected patients with peritoneal carcinomatosis. We review our institutional experience with the procedure and evaluate the overall survival (OS) and disease-free survival (DFS) rates in 100 consecutive patients. METHODS: Data were prospectively collected from 100 consecutive patients with peritoneal carcinomatosis treated by CRS and HIPEC at the National Cancer Centre Singapore between April 2001 and May 2012. Our primary end points were OS and DFS. RESULTS: Of the 100 patients, 84 were of Chinese ethnicity, 3 were Malay, 6 were Indian, and 7 were of other ethnicities. Primary tumors were ovarian cancer (n=39), colorectal cancer (n=28), primary peritoneal (n=6), appendiceal cancer (n=20), and mesothelioma (n=7). Median follow-up duration was 21 months. At 5 years, the DFS was 26.3% and OS was 50.9%. Factors influencing OS and DFS were cytoreductive score, primary cancer, and disease-free interval of more than 12 months on univariate analysis. The only factors that remained significant for prognosis after multivariate analysis were primary cancer and cytoreductive score. Thirty-day morbidity was 56%, and there were no 30-day mortalities. CONCLUSIONS: CRS and HIPEC can be safely carried out in Asian patients with peritoneal carcinomatosis from ovarian, colorectal, appendiceal, mesothelioma, and primary peritoneal origins. Overall, the ovarian, appendiceal, mesothelioma, and primary peritoneal cancer patients tended to do better than the colorectal patients, but careful patient selection ensuring that optimal cytoreduction can be achieved is essential for the success of this procedure.
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Neoplasias del Apéndice/mortalidad , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/mortalidad , Hipertermia Inducida , Mesotelioma/mortalidad , Neoplasias Ováricas/mortalidad , Neoplasias Peritoneales/mortalidad , Complicaciones Posoperatorias , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mesotelioma/patología , Mesotelioma/terapia , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Cuidados Posoperatorios , Pronóstico , Estudios Prospectivos , Singapur , Tasa de Supervivencia , Adulto JovenRESUMEN
Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we used a conventional lentiviral transduction method to derive human-induced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole-body imaging technology, we demonstrated that after tail vein injection, these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor-bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumor-bearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help to overcome problems associated with allogeneic transplantation of other types of human NSCs.
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Células Madre Pluripotentes Inducidas/trasplante , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/terapia , Células-Madre Neurales/trasplante , Trasplante de Células Madre , Animales , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Modelos Animales de Enfermedad , Femenino , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Especificidad de Órganos , Trasplante HeterólogoRESUMEN
OBJECTIVE: To identify methylated genes in serum with diagnostic potentials for early colorectal cancer (CRC). METHODS: Serum methylation levels of up to 12 genes were measured in two sets of serum samples with the second set from 26 stage I CRC patients and 26 age/gender-matched controls. RESULTS: Serum methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants between stage I CRC and healthy controls. Combination of TAC1 and SEPT9 rendered 73.1% sensitivity with 92.3% specificity. CONCLUSION: Serum methylation levels of TAC1. SEPT9 and EYA4 may be useful biomarkers for early detection of CRC though a validation study is necessary.
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Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/sangre , Septinas/sangre , Transactivadores/sangre , Proteína Activadora Transmembrana y Interactiva del CAML/sangre , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Metilación de ADN , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , Estudios Prospectivos , Curva ROC , Septinas/genética , Transactivadores/genética , Proteína Activadora Transmembrana y Interactiva del CAML/genéticaRESUMEN
Using neural stem cells (NSCs) with tumor tropic migratory capacity to deliver therapeutic genes is an attractive strategy in eliminating metastatic or disseminated tumors. While different methods have been developed to isolate or generate NSCs, it has not been assessed whether induced pluripotent stem (iPS) cells, a type of pluripotent stem cells that hold great potential for regenerative medicine, can be used as a source for derivation of NSCs with tumor tropism. In this study, we used a conventional lentivirus transduction method to derive iPS cells from primary mouse embryonic fibroblasts and then generated NSCs from the iPS cells. To investigate whether the iPS cell derived NSCs can be used in the treatment of disseminated brain tumors, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected into the cerebral hemisphere contralateral to a tumor inoculation site in a mouse intracranial human glioma xenograft model. We observed that NSCs expressing the suicide gene were, in the presence of ganciclovir, effective in inhibiting the growth of the glioma xenografts and prolonging survival of tumor-bearing mice. Our findings provide evidence for the feasibility of using iPS cell derived NSCs as cellular vehicles for targeted anticancer gene therapy.
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Técnicas de Transferencia de Gen , Glioma/terapia , Células Madre Pluripotentes Inducidas/fisiología , Células-Madre Neurales/trasplante , Animales , Antineoplásicos/uso terapéutico , Células Cultivadas , Terapia Combinada , Embrión de Mamíferos/citología , Estudios de Factibilidad , Femenino , Genes Transgénicos Suicidas , Glioma/tratamiento farmacológico , Glioma/patología , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/virología , Ratones , Ratones Endogámicos , Ratones Desnudos , Células-Madre Neurales/citología , Células-Madre Neurales/virología , Prosencéfalo/citología , Prosencéfalo/efectos de los fármacos , Prosencéfalo/patología , Simplexvirus/enzimología , Análisis de Supervivencia , Timidina Quinasa/genética , Timidina Quinasa/metabolismo , Timidina Quinasa/uso terapéutico , Proteínas Virales/genética , Proteínas Virales/metabolismo , Proteínas Virales/uso terapéutico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: We present the strategy of a comprehensive cancer center organized to make operations pandemic proof and achieve continuity of cancer care during the COVID-19 pandemic. METHODS: Disease Outbreak Response (DORS) measures implemented at our center and its satellite clinics included strict infection prevention, manpower preservation, prudent resource allocation, and adaptation of standard-of-care treatments. Critical day-to-day clinical operations, number of persons screened before entry, staff temperature monitoring, and personal protection equipment stockpile were reviewed as a dashboard at daily DORS taskforce huddles. Polymerase chain reaction swab tests performed for patients and staff who met defined criteria for testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were tracked. Descriptive statistics of outpatient attendances and treatment caseloads from February 3 to May 23, 2020, were compared with the corresponding period in 2019. RESULTS: We performed COVID-19 swabs for 80 patients and 93 staff, detecting three cancer patients with community-acquired COVID-19 infections with no nosocomial transmission. Patients who required chemotherapy, radiotherapy, or surgery and patients who are on maintenance treatment continued to receive timely treatment without disruption. The number of intravenous chemotherapy treatments was maintained at 97.8% compared with 2019, whereas that of weekly radiotherapy treatments remained stable since December 2019. All cancer-related surgeries proceeded without delay, with a 0.3% increase in workload. Surveillance follow-ups were conducted via teleconsultation, accounting for a 30.7% decrease in total face-to-face clinic consultations. CONCLUSION: Through the coordinated efforts of a DORS taskforce, it is possible to avoid nosocomial SARS-CoV-2 transmissions among patients and staff without compromising on care delivery at a national cancer center.
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Comités Consultivos , COVID-19/prevención & control , Instituciones Oncológicas/organización & administración , Continuidad de la Atención al Paciente/organización & administración , Control de Infecciones/organización & administración , Atención Ambulatoria/organización & administración , COVID-19/epidemiología , COVID-19/transmisión , Prueba de Ácido Nucleico para COVID-19 , Infecciones Comunitarias Adquiridas/epidemiología , Infección Hospitalaria/epidemiología , Asignación de Recursos para la Atención de Salud , Personal de Salud , Hospitalización , Humanos , Tamizaje Masivo , Equipo de Protección Personal/provisión & distribución , SARS-CoV-2 , Singapur/epidemiologíaRESUMEN
BACKGROUND: During the ongoing COVID-19 pandemic, healthcare-associated transmission of respiratory viral infections (RVI) is a concern. To reduce the impact of SARS-CoV-2 and other respiratory viruses on patients and healthcare workers (HCWs) we devised and evaluated a multi-tiered infection control strategy with the goal of preventing nosocomial transmission of SARS-CoV2 and other RVIs across a large healthcare campus. METHODS: From January-June 2020, a multi-tiered infection control strategy was implemented across a healthcare campus in Singapore, comprising the largest acute tertiary hospital as well as four other subspecialty centres, with more than 10,000 HCWs. Drawing on our institution's experience with an outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003, this strategy included improved patient segregation and distancing, and heightened infection prevention and control (IPC) measures including universal masking. All symptomatic patients were tested for COVID-19 and common RVIs. RESULTS: A total of 16,162 admissions campus-wide were screened; 7.1% (1155/16,162) tested positive for COVID-19. Less than 5% of COVID-19 cases (39/1155) were initially detected outside of isolation wards in multi-bedded cohorted wards. Improved distancing and enhanced IPC measures successfully mitigated onward spread even amongst COVID-19 cases detected outside of isolation. COVID-19 rates amongst HCWs were kept low (0.13%, 17/13,066) and reflected community acquisition rather than nosocomial spread. Rates of healthcare-associated-RVI amongst inpatients fell to zero and this decrease was sustained even after the lifting of visitor restrictions. CONCLUSION: This multi-tiered infection control strategies can be implemented at-scale to successfully mitigate healthcare-associated transmission of respiratory viral pathogens.
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COVID-19/prevención & control , Infección Hospitalaria/prevención & control , Infecciones del Sistema Respiratorio/prevención & control , SARS-CoV-2 , Personal de Salud , HumanosRESUMEN
BACKGROUND: Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma. METHODS: Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov, NCT03033446 and has been completed. FINDINGS: 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4-48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3-4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites). INTERPRETATION: Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread. FUNDING: National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex.
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Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Nivolumab/uso terapéutico , Radioisótopos de Itrio/uso terapéutico , Administración Intravenosa , Adulto , Anciano , Carcinoma Hepatocelular/diagnóstico , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/patología , Masculino , Microesferas , Persona de Mediana Edad , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Supervivencia sin Progresión , Seguridad , Índice de Severidad de la Enfermedad , Singapur/epidemiología , Resultado del Tratamiento , Radioisótopos de Itrio/administración & dosificación , Radioisótopos de Itrio/metabolismoRESUMEN
INTRODUCTION: The educational environment (EE) reflects the quality of a residency programme and has an association with burnout. Studying the EE allows for interventions to target specific weaknesses. We aimed to measure the EE of an internal medicine residency programme in Singapore, compare the perceptions between genders, residency grades and levels of work experience, and identify specific areas of weaknesses for intervention in hopes of reducing residency burnout rates in Singapore. METHODS: This study took place between October and December 2017. We adopted a mixed methods approach, quantitatively using the Postgraduate Hospital Educational Environment Measure (PHEEM), and qualitative exploration using semi-structured focus group discussion. RESULTS: A total of 136 (88.9%) out of 153 residents responded. Our total PHEEM scores (112.23 ± 16.71), along with the scores for all three subscales, were higher than those of institutions in previous studies. There were no differences in overall PHEEM and subscale scores between genders, residency grades or levels of work experience. However, there were differences for individual questions, which were explored in the focus group discussion. Senior residents juggling heavier workloads, responsibilities and examinations appeared to be most prone to burnout. We identified three recurring themes that contributed to a poor EE in our programme: excessive workload, poor faculty relationships and differing unmet needs. CONCLUSION: Although our programme had a good EE, there were also areas of weaknesses revealed by specific questions, possibly contributing to burnout. We hope to implement interventions to these areas and subsequently assess for longitudinal changes in EE and burnout rates.
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Agotamiento Profesional , Internado y Residencia , Agotamiento Profesional/prevención & control , Femenino , Humanos , Masculino , Singapur , Encuestas y Cuestionarios , Carga de TrabajoRESUMEN
AIM: The survival benefit of using a non-cross resistant second-line chemotherapy in the third-line setting in metastatic gastroesophageal cancer is unproven. We evaluated the utility of third-line chemotherapy in patients treated at a single institution. METHODS: Between 2010 and 2014, efficacy and toxicity data of patients who received three or more lines of systemic therapies for metastatic gastroesophageal adenocarcinoma at the National Cancer Centre Singapore was retrospectively analyzed. RESULTS: Thirty-two (6%) patients received three or more lines of chemotherapy. The median age and ECOG performance status were 59 years (36-82) and 1 (0-2), respectively. Majority of patients (88%) had tumor located in the stomach and 13 patients (41%) had diffuse histology or poorly cohesive or signet ring cells. Four (12%) patients had HER2-positive disease. Prior therapy was platinum (100%), fluoropyrimidine (97%), taxane (63%), irinotecan (28%), anthracycline (13%) and ramucirumab (3%). Third-line therapy consisted of 24 (75%) monotherapy, 6 (19%) doublet, 1 (3%) triplet chemotherapy and 1 (3%) clinical trial. Monotherapy irinotecan (44%) was most common, followed by docetaxel (19%) and paclitaxel (9%). Of 22 patients evaluable for response, there was 1 (5%) partial response, 9 (41%) stable disease. Median overall survival was 18.3 weeks (4.3-65.1). Of 30 patients evaluable for toxicities, 17 (57%) experienced at least one grade 3 or 4 toxicities. CONCLUSION: The benefit of using non-cross resistant second-line regimens as third-line chemotherapy was small with moderate toxicity. Newer agents such as nivolumab or TAS-102 or clinical trial may be preferred.
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Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/mortalidad , Neoplasias Gástricas/mortalidad , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Singapur , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Tasa de Supervivencia , Factores de TiempoRESUMEN
The COVID-19 pandemic has disrupted current models of healthcare and adaptations will likely continue. With the gradual easing of lockdown measures worldwide, cancer centres must be prepared to implement novel means to prevent repeated waves of infection. There are two limitations unique to oncology - a higher susceptibility of patients to COVID-19 and the multidisciplinary approach required of cancer management. We describe the measures implemented in the largest cancer centre in Singapore to continue optimal cancer care in spite of the ongoing pandemic, with no nosocomial infections reported in our centre to date. We adopted a multipronged approach, with an overall committee supervising the entire COVID-19 management effort. A screening clinic was setup to triage patients prior to entry to the centre. Each Oncology Division within the cancer centre designed solutions tailored to the specific needs of their discipline. We explore in detail the screening criteria and workflow of the screening clinic, as well as modifications by individual divisions to reduce infection risk to patients and healthcare professionals. This approach can be modelled by other cancer centres during this prolonged COVID-19 pandemic.
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BACKGROUND: Attributes of the clinical learning environment (CLE) are a measure of quality in postgraduate medical education, and assessing the CLE is a component of the New Accreditation System being introduced in Singapore by the Accreditation Council for Graduate Medical Education International. There is a dearth of published studies of CLE quality in Singapore. OBJECTIVE: Our study had 3 aims: (1) to measure the CLE in 1 Singaporean residency program; (2) to compare trainee perceptions by sex, training level, and experience; and (3) to identify areas for improvement. METHODS: Between October and December 2017, we conducted a mixed assessment of the CLE in an internal medicine program in Singapore, using the Postgraduate Hospital Educational Environment Measure (PHEEM) and qualitative exploration using a focus group. RESULTS: Of 153 IM residents, 136 (89%) provided PHEEM responses and 8 participated in the focus group. Total PHEEM scores and scores for the 3 subscales were higher than published data on the use of the PHEEM in international settings. Exploration of selected PHEEM responses via a focus group identified attributes associated with negative perceptions of the CLE: excessive workload, inadequate faculty presence in the CLE, and unmet trainee needs. It also suggested senior residents' clinical workloads, greater responsibilities, and pending examinations may contribute to their less positive perceptions of the CLE. CONCLUSIONS: Our analysis using the PHEEM showed overall positive perceptions of the CLE, along with areas for improvement amenable to interventions. Our approach has relevance to an accreditation model with ongoing evaluation of the CLE.
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Acreditación/normas , Medicina Interna/educación , Internado y Residencia , Mejoramiento de la Calidad , Adulto , Educación de Postgrado en Medicina , Femenino , Grupos Focales , Humanos , Masculino , Singapur , Encuestas y Cuestionarios , Carga de Trabajo/psicologíaRESUMEN
AIM: We aimed to compare the frequencies, clinical characteristics, and prognostic factors of peripheral T-cell lymphoma (PTCL) vs. extra-nodal natural killer (NK)/T-cell lymphoma and to characterize the subtypes of extra-nodal NK/T-cell lymphoma. METHODS: We reviewed 97 consecutive patients with PTCL and extra-nodal NKT lymphoma from 2000 to 2006. During this period, a total of 780 patients with malignant lymphomas were treated in our center. The diagnostic criteria used were based on the WHO classification system of malignant lymphomas. RESULTS: Extra-nodal-NK/T-cell lymphoma and PTCL comprised 5.0% (39/780) and 7.4% (58/780) of all cases. Of the PTCL cases, histology was PTCL-NOS in 25, anaplastic large cell in 11, angioimmunoblastic T cell in 18 and other subtypes in four patients. Compared with PTCL, extra-nodal NK/T-cell lymphoma was associated with a significantly inferior rates of complete remission (33% vs. 53%, P = 0.05) and 3 yr overall survival (29.5% vs. 47.5%, P = 0.003). On multivariate analysis, extra-nodal NK/T-cell histology was independently associated with decreased survival. Further analysis into this subtype showed the nasal variant (n = 25) differed significantly from extra-nasal variant (n = 14) in terms of stage at presentation (stages III/IV, 36% vs. 79%), international prognostic index scores (high intermediate or high IPI scores, 24% vs. 64%), complete remission rates (48% vs. 7%), and median survival (10 months vs. 1 month, P < 0.0001). CONCLUSIONS: Extra-nodal NK/T-cell lymphoma was associated with a poorer prognosis compared with PTCL and is likely to comprise two distinct variants with different clinical behavior and prognosis.
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Células Asesinas Naturales/patología , Linfoma de Células T Periférico/patología , Linfoma de Células T/patología , Distribución por Edad , Femenino , Humanos , Linfoma de Células T/epidemiología , Linfoma de Células T/mortalidad , Linfoma de Células T Periférico/epidemiología , Linfoma de Células T Periférico/mortalidad , Masculino , Neoplasias Nasales/mortalidad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) are inoperable and results with conventional chemotherapy are dismal. Many end up with no treatment options and resort to alternative medicine. The authors report the use of Coriolus versicolor (CV) in advanced HCC patients with poor liver function or who were unfit to receive standard therapy. METHODS: Fifteen eligible cases were randomized 2:1 to either CV or placebo. The primary endpoint was the median time to progression (TTP) between both arms. Secondary endpoints include evaluating response rates, toxicity, quality of life (QOL), progression-free survival (PFS), and overall survival (OS). Further correlative studies were performed looking at the effect of CV on the immune system. RESULTS: The median treatment duration was 1.5 cycles and 3 cycles on the placebo and CV arm, respectively. Median TTP was 2.5 (1.4-5.3) months compared to 4.2 (0.4-4.2) months in the CV and placebo arm, respectively, hazard ratio (HR) 0.70 (0.16-3.05 p = 0.634). Median PFS was 2.5 (1.4-5.3) months in the CV and 1.1 (0.4-4.2) months in the placebo arm, HR 0.42 (0.13-1.34, p = 0.144). Median OS was 6.5 (3.3-24.1) and 2.2 (0.8-23.3) months, respectively, HR 0.35 (0.10-1.25, p = 0.105). Social and emotional functioning scores were higher in the CV group compared to placebo group on treatment. CV subjects had less appetite loss and pain symptoms compared to placebo subjects during treatment. CONCLUSIONS: There was no difference in TTP with use of CV compared to placebo. CV subjects generally had better QOL on treatment compared to placebo subjects. The utility of this supplement in patients whose primary treatment goal is palliation should be further explored.
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Basidiomycota , Productos Biológicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Anciano , Carcinoma Hepatocelular/fisiopatología , Femenino , Humanos , Hígado/fisiopatología , Neoplasias Hepáticas/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
IMPORTANCE: Hand-foot syndrome (HFS) is a common adverse effect of capecitabine treatment. OBJECTIVE: To compare the incidence and time to onset of grade 2 or greater HFS in patients receiving pyridoxine vs placebo and to identify biomarkers predictive of HFS. DESIGN, SETTING, AND PARTICIPANTS: This single-center, randomized double-blind, placebo-controlled phase 3 trial conducted at National Cancer Centre Singapore assessed whether oral pyridoxine could prevent the onset of grade 2 or higher HFS in 210 patients scheduled to receive single-agent capecitabine chemotherapy for breast, colorectal, and other cancers. INTERVENTIONS: Patients were randomized to receive concurrent pyridoxine (200 mg) or placebo daily for a maximum of 8 cycles of capecitabine, with stratification by sex and use in adjuvant or neoadjuvant vs palliative setting. Patients were withdrawn from the study on development of grade 2 or higher HFS or cessation of capecitabine. MAIN OUTCOMES AND MEASURES: Primary end point was the incidence of grade 2 or higher HFS in patients receiving pyridoxine. Secondary end points included the time to onset (days) of grade 2 or higher HFS and identification of biomarkers predictive of HFS, including baseline folate and vitamin B12 levels, as well as genetic polymorphisms with genome-wide arrays. RESULTS: In this cohort of 210 patients (median [range] age, 58 [26-82] years; 162 women) grade 2 or higher HFS occurred in 33 patients (31.4%) in the pyridoxine arm vs 39 patients (37.1%) in the placebo arm (P = .38). The median time to onset of grade 2 or higher HFS was not reached in both arms. In univariate analysis, the starting dose of capecitabine (odds ratio [OR], 1.99; 95% CI, 1.32-3.00; P = .001), serum folate levels (OR, 1.27; 95% CI, 1.10-1.47; P = .001), and red blood cell folate levels (OR, 1.25; 95% CI, 1.08-1.44; P = .003) were associated with increased risk of grade 2 or higher HFS. In multivariate analyses, serum folate (OR, 1.30; 95% CI, 1.12-1.52; P < .001) and red blood cell folate (OR, 1.28; 95% CI, 1.10-1.49; P = .001) were the only significant predictors of grade 2 or higher HFS. Grade 2 or higher HFS was associated with 300 DNA variants at genome-wide significance (P < 5 × 10-8), including a novel DPYD variant (rs75267292; P = 1.57 × 10-10), and variants in the MACF1 (rs183324967, P = 4.80 × 10-11; rs148221738, P = 5.73 × 10-10) and SPRY2 (rs117876855, P < 1.01 × 10-8; rs139544515, P = 1.30 × 10-8) genes involved in wound healing. CONCLUSIONS AND RELEVANCE: Pyridoxine did not significantly prevent or delay the onset of grade 2 or higher HFS. Serum and red blood cell folate levels are independent predictors of HFS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00486213.