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BACKGROUND: Reviewing experiences and recognizing the impact of personal and professional views and emotions upon conduct shapes a physician's professional and personal development, molding their professional identity formation (PIF). Poor appreciation on the role of reflection, shortages in trained tutors and inadequate 'protected time' for reflections in packed medical curricula has hindered its integration into medical education. Group reflection could be a viable alternative to individual reflections; however, this nascent practice requires further study. METHODS: A Systematic Evidence Based Approach guided Systematic Scoping Review (SSR in SEBA) was adopted to guide and structure a review of group reflections in medical education. Independent searches of articles published between 1st January 2000 and 30th June 2022 in bibliographic and grey literature databases were carried out. Included articles were analysed separately using thematic and content analysis, and combined into categories and themes. The themes/categories created were compared with the tabulated summaries of included articles to create domains that framed the synthesis of the discussion. RESULTS: 1141 abstracts were reviewed, 193 full-text articles were appraised and 66 articles were included and the domains identified were theories; indications; types; structure; and benefits and challenges of group reflections. CONCLUSIONS: Scaffolded by current approaches to individual reflections and theories and inculcated with nuanced adaptations from other medical practices, this SSR in SEBA suggests that structured group reflections may fill current gaps in training. However, design and assessment of the evidence-based structuring of group reflections proposed here must be the focus of future study.
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Educação Médica , Humanos , Currículo , EmoçõesRESUMO
Worldwide advances in treatment and supportive care for children and adolescents with cancer have resulted in a increasing population of survivors growing into adulthood. Yet, this population is at very high risk of late occurring health problems, including significant morbidity and early mortality. Unique barriers to high-quality care for this group include knowledge gaps among both providers and survivors as well as fragmented health-care delivery during the transition from paediatric to adult care settings. Survivors of childhood and adolescent cancer are at risk for a range of late-occuring side-effects from treatment, including cardiac, endocrine, pulmonary, fertility, renal, psychological, cognitive, and socio-developmental impairments. Care coordination and transition to adult care are substantial challenges, but can be empowering for survivors and improve outcomes, and could be facilitated by clear, effective communication and support for self-management. Resources for adult clinical care teams and primary care providers include late-effects surveillance guidelines and web-based support services.
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Neoplasias , Transição para Assistência do Adulto , Adolescente , Adulto , Criança , Atenção à Saúde , Humanos , Assistência de Longa Duração , Neoplasias/terapia , SobreviventesRESUMO
Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with R/R TCL and NKTL were treated with standard dose ICE, dexamethasone 20mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose level (DL) 1, 2 and 3 were 40, 60 and 80mg respectively. Eleven patients with a median age of 60 were enrolled; 6 at DL1 and 5 at DL2. Patients had received a median of 2 (range 1-4) prior lines of treatment and 7 had primary refractory disease at study entry. Patients received a median of 3 cycles (range 1-6) of selinexor-DICE. The most common grade (G) 1/2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common G 3/4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed doselimiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the 10 evaluable patients, the overall and complete response rates were 91% and 82% respectively. The MTD of selinexor was 40mg when combined with DICE. The combination showed promising CR rates in patients with R/R TCL and NKTL but was poorly tolerated.
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Ifosfamida , Linfoma de Células T , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Dexametasona , Etoposídeo/efeitos adversos , Humanos , Hidrazinas , Ifosfamida/efeitos adversos , Recidiva Local de Neoplasia , TriazóisRESUMO
BACKGROUND: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. METHODS: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. RESULTS: The median age of the cohort was 59 years (range, 26-84), with a male predominance (73%). The majority (86%) had advanced stage 3-4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48-7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10-5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21-4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17-4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16-0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. CONCLUSIONS: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.
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Anemia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Hipoalbuminemia/epidemiologia , Linfoma de Célula do Manto/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/diagnóstico , Anemia/etiologia , Citarabina/administração & dosagem , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Hipoalbuminemia/sangue , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/etiologia , Quimioterapia de Indução/métodos , Quimioterapia de Indução/estatística & dados numéricos , Estimativa de Kaplan-Meier , Linfoma de Célula do Manto/sangue , Linfoma de Célula do Manto/complicações , Linfoma de Célula do Manto/mortalidade , Quimioterapia de Manutenção/métodos , Quimioterapia de Manutenção/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Rituximab/administração & dosagem , Singapura/epidemiologia , Transplante Autólogo/estatística & dados numéricosRESUMO
OBJECTIVE: Cancer-related cognitive impairment (CRCI) among adolescent and young adult (AYA) cancer patients with noncentral nervous system (CNS) cancers has not been well studied. In this study, we aimed to describe CRCI-associated trends and characteristics among AYA cancer patients. METHODS: In a longitudinal cohort of AYA cancer patients without CNS disease, CRCI was evaluated over 1 year using the Functional Assessment of Cancer Therapy-Cognitive Function Instrument, a self-reported cognitive outcome measure. CRCI prevalence was quantified using the previously established minimal clinically important difference. CRCI-associated longitudinal trends and factors were evaluated with mixed-effects model analysis. RESULTS: Ninety-one patients (mean age = 28.4 ± 6.7 years) were included. Approximately one-third (34.1%) experienced CRCI at least once during the study follow-up. Female gender (P = .02), Indian ethnicity (P < .01), current smokers (P < .01), anxiety/depressive symptoms (P < .01) and fatigue (P < .01) were found to be associated with poorer cognitive function among AYAs. CONCLUSIONS: Although AYA cancer patients were relatively young and without CNS disease involvement, a significant proportion of them experienced clinically important decline in cognitive function. With improved understanding of this subject, effective strategies can be formulated to promote awareness of CRCI and mitigate its negative effects among AYA cancer patients.
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Ansiedade/psicologia , Sobreviventes de Câncer/psicologia , Disfunção Cognitiva/psicologia , Neoplasias/psicologia , Autorrelato , Adolescente , Ansiedade/etiologia , Cognição , Disfunção Cognitiva/etiologia , Fadiga/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Adulto JovemRESUMO
PURPOSE: Work-related issues among Asian adolescent and young-adult (AYA) cancer survivors are poorly described in the literature. There has also been a paucity of reports regarding insurance-related concerns in this patient population. Focus groups were therefore carried out in Singapore to understand survivorship issues related to work and insurance coverage among Asian AYA cancer survivors. METHODS: Twenty-three AYA survivors and 18 healthcare professionals (HCPs) who care for AYA cancer patients were recruited for 11 focus group sessions. Thematic content analysis was carried out to identify major themes that emerged. RESULTS: Similar themes emerged from AYA and HCP focus groups. The majority of AYA survivors were eager to return to work post-treatment. However, some survivors were worried about not keeping up with expectations and struggled with disclosure of their medical history. In contrast, several survivors leveraged on their experience with cancer to bolster job opportunities. Despite facing challenges due to complications from cancer and restrictions at work, AYA survivors preferred to be treated normally. AYA survivors also expressed concerns about inadequate insurance coverage and a lack of information on this topic. CONCLUSION: Contrary to expectations, Asian AYA survivors are motivated to return to work and address work-related challenges. Inadequate insurance coverage remains a pressing concern despite the availability of public health insurance and subsidies. Career coaches and financial counselors should be incorporated into survivorship care to aid AYA survivors.
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Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Neoplasias/psicologia , Retorno ao Trabalho/psicologia , Engajamento no Trabalho , Adolescente , Adulto , Povo Asiático , Feminino , Grupos Focais , Pessoal de Saúde/psicologia , Humanos , Masculino , Neoplasias/terapia , Pesquisa Qualitativa , Singapura , Sobrevivência , Adulto JovemRESUMO
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/psicologia , Estresse Psicológico/psicologia , Adolescente , Adulto , Povo Asiático , Feminino , Humanos , Estudos Longitudinais , Masculino , Programas de Rastreamento , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Sarcomas are heterogeneous rare cancers, and while they affect 1% of all adult cancers, they affect 10-20% of adolescents and young adults (AYAs). The 5-year survival rates range between 50-60% but have remained stagnant. While the management of bony sarcomas (BS) usually involves systemic treatment and major morbid surgeries, functional outcomes and quality of life have been largely overlooked. METHODS: A literature search was conducted on PubMed and ScienceDirect using key search terms of "Adolescent and young adult", "AYAO", "bone sarcoma, osteosarcoma, Ewing sarcoma", "functional outcomes" and "health-related quality of life" from 1st January 2003 to 13 March 2023. A total of 858 results in total were screened by two independent authors, and 18 selected papers were included in the scoping review. RESULTS: AYAs have poorer outcomes in all aspects-physical, social and psychological in BS survivorship, as many changes from disease and treatment are usually persistent and irreversible, with significant impact on mobility, function and body image. Current tools to assess health-related quality of life (HRQoL) in AYAs are not standardized or validated in this age group. Subjective tools measuring physical outcomes do not correlate to objective measures of physical function. CONCLUSIONS: These outcomes have a direct connection to their independence, self-confidence and future job endeavors, yet hardly any specific research has gone into it. They are stricken with a cancer diagnosis during the prime of their lives and it is essential to manage them holistically to preserve and maximize their functional outcomes. More research is required to monitor their outcomes long-term post-treatment and into survivorship.
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Qualidade de Vida , Sarcoma , Humanos , Adolescente , Adulto Jovem , Sarcoma/terapia , Masculino , Neoplasias Ósseas/psicologia , Neoplasias Ósseas/terapia , Feminino , AdultoRESUMO
The use of central nervous system (CNS) prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) remains controversial. Although uncommon, CNS relapses are invariably fatal in this otherwise curable disease. Accurate identification of patients at risk and the optimal approach to CNS prophylaxis therefore remains an area of unmet need. The existing literature, largely retrospective in nature, provides mixed conclusions regarding the efficacy of CNS prophylaxis. The utility of CNS prophylaxis has itself been challenged. In this review, we dissect the issues which render the value of CNS prophylaxis uncertain. We first compare international clinical guidelines for CNS prophylaxis. We then interrogate the factors that should be used to identify high-risk patients accurately. We also explore how clinical patterns of CNS relapse have changed in the pre-rituximab and rituximab era. We then discuss the efficacy of CNS-directed approaches, intensification of systemic treatment and other novel approaches in CNS prophylaxis. Improved diagnostics for early detection of CNS relapses and newer therapeutics for CNS prophylaxis are areas of active investigation. In an area where prospective, randomized studies are impracticable and lacking, guidance for the use of CNS prophylaxis will depend on rigorous statistical review of retrospective data.
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BACKGROUND: The most common aggressive lymphoma in adults is diffuse large B-cell lymphoma (DLBCL). Consolidative radiotherapy (RT) is often administered to DLBCL patients but guidelines remain unclear, which could lead to unnecessary RT. We aimed to evaluate the value of end-of-treatment PET-CT scans, interpreted using the Deauville score (DV), to guide the utilization of consolidative RT, which may help spare low-risk DLBCL patients from unnecessary RT. METHODS: We included all DLBCL patients diagnosed between 2010 and 2022 at the National Cancer Centre Singapore with DV measured at the end of the first-line chemoimmunotherapy. The outcome measure was time-to-progression (TTP). The predictive value of DV for RT was assessed based on the interaction effect between the receipt of RT and DV in Cox regression models. RESULTS: The data of 349 patients were analyzed. The median follow-up time was 38.1 months (interquartile range 34.0-42.3 months). RT was associated with a significant improvement in TTP amongst the DV4-5 patients (HR 0.33; 95%CI 0.13-0.88; p = 0.027) but not the DV1-3 patients (HR 0.85; 95%CI 0.40-1.81; p = 0.671) (interaction's p = 0.133). Multivariable analysis reported that RT was again significantly associated with improved TTP among the DV4-5 patients (adjusted HR 0.29; 95%CI 0.10-0.80; p = 0.017) but not the DV1-3 group (HR 0.86; 95%CI 0.40-1.86; p = 0.707) (interaction's p = 0.087). CONCLUSION: Our results suggests that DLBCL patients with end-of-treatment PET-CT DV1-3 may not need consolidative RT. Longer follow-up and prospective randomized trials are still necessary to investigate long-term outcomes.
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Dermatofibrosarcoma protuberans (DFSP) is a rare and indolent cutaneous sarcoma, with the risk of aggressive fibro-sarcomatous transformation. Limited effective options are available for un-resectable or metastatic DFSP beyond targeting the oncogenic PDGF pathway with imatinib therapy. We established a patient-derived xenograft (PDX) and cell line model (designated MDFSP-S1) of imatinib-resistant DFSP with fibro-sarcomatous transformation. Whole genome sequencing identified high-level amplification at chromosomes 17 and 22, whilst homozygous deep deletion was demonstrated at chromosome 9 (CDKN2A, CDKN2B, MTAP). RNA sequencing followed by Sanger sequencing confirmed the pathognomonic COL1A1-PDGFB t (17;22) rearrangement in the original tumour, PDX and cell line model. Immunohistochemistry profiles of the PDX model were consistent with the patient's tumour sample (CD34 + /MIB1 + /SOX10- ). Gene set enrichment analysis highlighted top-scoring Hallmark gene sets in several oncogenic signalling pathways, including potentially targetable MTORC1 signalling and angiogenesis pathways. Antiangiogenic agents (sunitinib, regorafenib, pazopanib, axitinib) and the third-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib exhibited modest anti-proliferative activity in the cell line, with IC50 values between 1 and 10 µM at 72 h. No significant activity was observed with imatinib, palbociclib, everolimus, olaparib, gefitinib and erlotinib (IC50 all > 10 µM). In conclusion, we established MDFSP-S1, a new PDX and cell line model of imatinib-resistant DFSP with fibro-sarcomatous transformation.
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Purpose: To quantify and evaluate trends of work outcomes and medical costs among Singaporean adolescent and young adult (AYA) cancer survivors. Methods: This cross-sectional study was conducted at the National Cancer Centre Singapore between July 2016 and October 2018. Cancer patients who were diagnosed between the age of 15 and 39 years and had completed treatment were eligible. Siblings of cancer patients were recruited as controls. Work outcomes were collected using an investigator-designed questionnaire, while cost data were extracted from the hospital database. Descriptive statistics were used to quantify work and cost outcomes. Mixed-effects logistic regression was used to compare employment rates between survivors and controls. Generalized linear models were used to characterize trends between medical costs and symptom burden. Results: A total of 29 cancer survivors and 23 sibling controls were analyzed. Approximately 80% of survivors and controls were employed at the time of survey; however, more than half of the employed survivors reported impaired work outcomes due to effects from cancer and cancer treatment, including work reallocation, absenteeism, and decreased work ability. Median productivity loss due to absenteeism in the past 3 months was estimated to be U.S. dollar (USD) 110. Total medical cost incurred within the first year after treatment completion remained high at a median of USD6592, with out-of-pocket expenditure between 17.2% and 100.0%. Conclusion: Despite their young age and having completed cancer treatment, Singaporean AYA cancer survivors may continue to experience poor work outcomes even after resuming work. High medical costs may also persist.
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Sobreviventes de Câncer , Neoplasias , Humanos , Adulto Jovem , Adolescente , Adulto , Efeitos Psicossociais da Doença , Estudos Transversais , Gastos em Saúde , Sobreviventes , Neoplasias/terapiaRESUMO
BACKGROUND: Post-intensive care unit (ICU) syndrome (PICS) occurs at an exorbitant rate in surgical ICU (SICU) survivors. It remains unknown if critical illness due to trauma versus acute care surgery (ACS) may represent different pathophysiologic entities. In this longitudinal study, we determined if admission criteria in a cohort of trauma and ACS patients were associated with differences in the occurrence of PICS. METHODS: Patients were 18 years or older, admitted to a Level I trauma center to the trauma or ACS services, remained in the SICU for ≥72 hours, and were seen in an ICU Recovery Center at 2 weeks, 12 weeks, and 24 weeks after hospital discharge. Post-ICU syndrome sequelae were diagnosed by dedicated specialist staffing using clinical criteria and screening questionnaires. The PICS symptoms were distilled into physical, cognitive, and psychiatric categories. Preadmission histories, hospital courses, and recovery data were collected via retrospective chart review. RESULTS: One hundred twenty-six patients were included: 74 (57.3%) trauma patients and 55 (42.6%) ACS patients. Prehospital psychosocial histories were similar between groups. Acute care surgery patients had a significantly longer hospital course, higher APACHE II and III scores, were intubated for longer, and had higher rates of sepsis, acute renal failure, open abdomen, and hospital readmissions. At the 2-week follow-up visit, ACS patients had higher rates of PICS sequelae (ACS, 97.8% vs. trauma 85.3%; p = 0.03), particularly in the physical (ACS, 95.6% vs. trauma 82.0%, p = 0.04), and psychiatric domains (ACS, 55.6% vs. trauma 35.0%, p = 0.04). At the 12-week and 24-week visits, rates of PICS symptoms were comparable between groups. CONCLUSION: The occurrence of PICS is extraordinarily high in both trauma and ACS SICU survivors. Despite entering the SICU with similar psychosocial histories, the two cohorts have different pathophysiologic experiences, which are associated with a higher rate of impairment in the ACS patients during early follow-up. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.
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Cuidados Críticos , Unidades de Terapia Intensiva , Humanos , Estudos Longitudinais , Estudos Retrospectivos , Progressão da Doença , SobreviventesRESUMO
We analyzed the prognostic factors for treatment outcomes amongst 34 patients with adult Burkitt lymphoma (BL) who received rituximab with standard first-line chemotherapy. Seven patients had human immunodeficiency virus (HIV)-associated BL. Overall, we observed a complete remission (CR) rate of 91.2%, and 10-year progression-free survival (PFS) and overall survival (OS) was 84.8 and 88.2%, respectively. In patients with concomitant HIV, the prognosis was not different with 10-year PFS of 100% and OS of 88.2%. The majority (71.4%) of HIV-associated BL patients received dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and had excellent outcomes with 100% CR and no relapses. Central nervous system (CNS) disease, bone marrow involvement and elevated serum lactate dehydrogenase (LDH) levels more than 3 times upper limit of normal (ULN) were associated with poorer survival outcomes. Patients with refractory disease, whilst uncommon (n = 4), had dismal outcomes. Patients with adult BL, including HIV-related cases, harbor generally good prognosis in the modern era.
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Linfoma de Burkitt , Infecções por HIV , Adulto , Humanos , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Rituximab , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Ciclofosfamida , Vincristina/efeitos adversos , Doxorrubicina/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológicoRESUMO
Hodgkin's lymphoma carries an excellent prognosis with modern chemotherapy, but a significant proportion of patients remain refractory to or relapse after first-line treatment. Immunological changes post-treatment, such as chemotherapy-induced neutropenia (CIN) or lymphopenia, have shown prognostic significance in multiple tumor types. Our study aims to investigate the prognostic value of immunologic changes in Hodgkin's lymphoma by examining the post-treatment lymphocyte count (pALC), neutrophil count (pANC) and the neutrophil-lymphocyte ratio (pNLR). Patients treated for classical Hodgkin's lymphoma at the National Cancer Centre Singapore using ABVD-based regimens were retrospectively analyzed. An optimal cut-off value for high pANC, low pALC and high pNLR in predicting progression-free survival was determined by receiver operating curve analysis. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional models. Overall OS and PFS were excellent, with a 5-year OS of 99.2% and a 5-year PFS of 88.2%. Poorer PFS was associated with high pANC (HR 2.99, p = 0.0392), low pALC (HR 3.95, p = 0.0038) and high pNLR (p = 0.0078). In conclusion, high pANC, low pALC and high pNLR confer a poorer prognosis for Hodgkin's lymphoma. Future studies should evaluate the potential of improving treatment outcomes by the adjustment of chemotherapy dose intensity based on post-treatment blood counts.
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In our Asian multicenter retrospective study, we investigated the clinical prognostic factors affecting the outcomes of AITL patients and identified a novel prognostic index relevant in the Asian context. In our 174-patient cohort, the median PFS and OS was 1.8 years and 5.6 years respectively. Age > 60, bone marrow involvement, total white cell count >12 × 109/L and raised serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3-4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). POD24 proved to be strongly prognostic (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies were performed and disparate immune cell profiles and cell signaling signatures were seen in the low risk group as compared to the intermediate and high risk groups.
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Linfadenopatia Imunoblástica , Linfoma de Células T , Humanos , Prognóstico , Linfoma de Células T/patologia , Estudos Retrospectivos , Linfadenopatia Imunoblástica/diagnóstico , Linfadenopatia Imunoblástica/patologia , Fatores de RiscoRESUMO
Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD). Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence. Methods: Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported. Results: A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32-0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03-1.84). Qualitative assessment of the remaining selected studies revealed equivocal results. Conclusions: Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary.
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Background: Ratios of differential blood counts (hematological indices, HIs) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSLs), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HIs could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HIs were calculated at three time-points: baseline (pre steroid), pre chemoimmunotherapy (post steroid) and post chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan−Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan−Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR ≥ 4.0, HR 0.42, 95% CI: 0.21−0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR ≥ 241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03), respectively, only. The decision-tree model using age ≤70, post-steroid NLR >4.0, and pre-steroid (baseline) NLR <2.5 and the division of patients into three risk profileslow, medium, and highachieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusion: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed for accurate and well-calibrated stratification into three risk groups.
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Diffuse large B-cell lymphoma is treated with anti-CD 20 and multi-drug chemotherapy for cure. Positron emission tomography (PET) scans are performed at end of treatment (EOT) to assess response. EOT Deauville scores (DS) are equivocal for treatment response in some situations, requiring physicians to determine the need for further investigations or treatment. Studies have suggested the delta maximum standardised uptake value (ΔSUVmax) to be superior to DS for assessment of metabolic response at interim PET, although its use at EOT PET, especially in cases of equivocal response, has yet to be established. We investigated whether ΔSUVmax could better discriminate prognosis than DS 3 or 4 at EOT. ΔSUVmax did not outperform DS. Combination of DS 3 and International Prognostic Index (IPI) <3 selects for patients with extremely low risk of disease progression (HR 0.06, 95% CI 0.01 to 0.62, p 0.018) compared to DS 4 and IPI ≥3.
Assuntos
Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Prognóstico , Projetos de Pesquisa , Estudos RetrospectivosRESUMO
BACKGROUND: Contemporary data of peripheral T-cell lymphoma (PTCL) and natural-killer/T-cell lymphoma (NKTL) patients treated with ifosfamide, carboplatin and etoposide (ICE) are limited. AIMS: We performed a retrospective analysis to estimate outcomes of ICE-treated PTCL and NKTL patients at three tertiary cancer centres in Singapore. METHODS AND RESULTS: Patients were identified through lymphoma databases from National Cancer Centre Singapore (NCCS), National University Hospital, Singapore (NUHS), and Singapore General Hospital (SGH). Responses and survival outcomes were determined from electronic medical records. A total of 75 patients with a median age of 50 were included. ICE was used as first-line treatment in 14 patients (19%) and as subsequent lines of treatment in 61 patients (81%). The overall response rates (ORR) for all patients was 63% (40% complete response [CR]). The ORR and CR in the first line were 86% and 64% respectively. At a median follow-up duration of 71.0 months, the median progression-free (PFS) and overall survival (OS) for all patients were 4.4 months (95%CI, 2.7-6.0) and 16 months (95%CI, 8.3-45.4) respectively. CONCLUSION: In summary, ICE showed high ORR but poor PFS in relapsed/refractory PTCL and NKTL. ORR of ICE in the first line setting appears better than real-world CHOP data and warrants further study.