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Adult acute myeloid leukemia (AML) patients under the age of 60 often receive similar intensive treatments, while outcomes between the adolescent and young adult (AYA) age group (18-39) and middle-aged adults (40-60 years) were seldom reported. We aim to study the characteristics and outcomes of AYA patients in comparison to middle-aged adults. A retrospective analysis was performed on AYA patients treated at Princess Margaret Cancer Center between 2008 and 2018. The primary outcomes include overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). A total of 174 AYA patients and 176 middle-aged patients were included, with propensity score matching adjusting for potential major confounders. Comparing AYA and middle-aged patients, 5-year OS rates were similar at 54.6â¯% vs. 56.5â¯% (p=0.91), CIR rates at 29.5â¯% vs. 23.1â¯% (p=0.31), and similar NRM rates. Notably, non-transplanted AYA patients had a significantly higher CIR (39.8â¯%) compared to middle-aged patients (19.6â¯%) (p=0.0324), with more primary refractory/early relapsing disease. An observed trend toward improved OS in AYA patients post-2015 coincided with FLAG-IDA and haploidentical transplant implementations. In conclusion, the study suggests that AYA patients, particularly those not undergoing transplantation, may benefit from more intensive treatment strategies, emphasizing the need for tailored approaches in this age group.
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Nucleophosmin-1 (NPM1)-mutated AML is a molecularly defined subtype typically associated with favorable treatment response and prognosis; however, its prognostic significance in AML evolving from an antecedent chronic myeloid malignancy is unknown. This study's primary objective was to determine the impact of mutated NPM1 on the prognosis of AML evolving from an antecedent chronic myeloid malignancy. We conducted a retrospective chart review including patients with NPM1-mutated de novo and sAML. sAML was defined as those with a preceding chronic-phase myeloid malignancy before diagnosis of AML. Of 575 NPM1-mutated patients eligible for inclusion in our study, 51 (8.9%) patients were considered to have sAML. The median time from diagnosis of NPM1-mutated chronic myeloid malignancy to sAML evolution was 3.6 months (0.5-79.3 months). No significant differences in leukemia-free (2-year LKFS 52.0% vs. 51.2%, p = .9922) or overall survival (2-year OS 56.3% vs. 49.4%, p = .4246) were observed between patients with NPM1-mutated de novo versus sAML. Our study suggests that evolution from a preceding myeloid malignancy is not a significant predictor of poor prognosis in the setting of an NPM1 mutation. Our study demonstrated a short time to progression to sAML in most patients, which further supports the consideration of NPM1 as an AML-defining mutation.
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Leucemia Mieloide Aguda , Mutación , Proteínas Nucleares , Nucleofosmina , Humanos , Proteínas Nucleares/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/diagnóstico , Pronóstico , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Evolución Clonal/genéticaRESUMEN
BACKGROUND: Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann's reversal procedure in the prediction of short-term postoperative complications. METHODS: A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne. Sarcopenia in our study was defined as a skeletal muscle index (SMI), calculated as Skeletal Muscle Area (SMA) /height2 < 38.5 cm2/m2 in women and < 52.4 cm2/m2 in men. RESULTS: Between 2010 and 2020, 47 patients (mean age 63.1 ± 12.3 years; male, n = 28 (59.6%) underwent body composition analysis. Twenty-one patients (44.7%) were sarcopenic, and 12 (25.5%) had evidence of sarcopenic obesity. The most common postoperative complication was surgical site infection (SSI) (n = 8, 17%). Sarcopenia (n = 7, 87.5%, p = 0.02) and sarcopenic obesity (n = 5, 62.5%, p = 0.02) were significantly associated with SSIs. The risks of developing an SSI were 8.7 times greater when sarcopenia was present. CONCLUSION: Sarcopenia and sarcopenic obesity were related to postoperative complications following Hartmann's reversal. Body composition measured by a validated AI algorithm may be a beneficial tool for predicting short-term surgical outcomes for these patients.
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Proctocolectomía Restauradora , Sarcopenia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Sarcopenia/complicaciones , Sarcopenia/diagnóstico , Estudios Retrospectivos , Inteligencia Artificial , Anastomosis Quirúrgica/métodos , Resultado del Tratamiento , Colostomía/efectos adversos , Proctocolectomía Restauradora/efectos adversos , Infección de la Herida Quirúrgica/etiología , Obesidad/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaAsunto(s)
Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Asparaginasa/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antineoplásicos/uso terapéuticoRESUMEN
This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.6%), febrile neutropenia (38.4%), and transaminitis (34.2%). AEs did not translate into significant differences concerning overall survival, leukemia-free survival, or early mortality. Furthermore, we observed a reduction in early mortality rates (11% vs. 20%) and an increase in median overall survival (54 vs. 48 months) compared to our previous data. These findings suggest that the utilization of a pediatric-inspired chemotherapy protocol, with ASP, is an effective and well-tolerated therapeutic option for older patients with Ph-negative ALL. However, it emphasizes the importance of diligent monitoring and close follow-up throughout treatment.
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Asparaginasa , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Anciano , Asparaginasa/efectos adversos , Estudios Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Polietilenglicoles/efectos adversosRESUMEN
BACKGROUNDS: The coronavirus disease 2019 (COVID-19) has led to major shifts in the management of colorectal cancer (CRC). This study aims to identify the impact and early outcomes of COVID-19 following CRC management at a tertiary referral center in Victoria, Australia. METHODS: This was a retrospective study, utilizing the Australian Comprehensive Cancer Outcomes and Research Database and inpatient records. Patients presenting for CRC management at our institution were identified coinciding with the first Victorian outbreak of COVID-19 (March 26 to September 26, 2020) (COVID). Management decisions including chemoradiotherapy utilization and surgical outcomes were analyzed within 6 months and compared with the corresponding period in 2019 (pre-COVID). RESULTS: A total of 276 patients were included in this study (147 pre-COVID period, 129 COVID period). During the COVID period, more patients (47.6% vs. 60.5%; p = 0.033) presented symptomatically and less for surveillance (10.9% vs. 2.3%; p < 0.01). Eighty-four pre-COVID and 69 COVID period patients proceeded to surgery. The average time from diagnosis date to surgery was 15.6 days less during the COVID period. There were no significant differences in postoperative utilization of higher care (p = 0.74), complications (p = 0.93), median hospital length of stay (p = 0.67), 30-day readmission (p = 0.50), or 30-day reoperation (p = 0.74). In 1.6% of cases, pandemic impacts resulted in a change in management. CONCLUSION: Presentation of patients with CRC varied, with a significant increase in symptomatic presentations and decreased numbers for surveillance. Through flexibility and change in practice, our institution helped improve access to surgical intervention and oncological therapies. Further prospective work is required to identify long-term outcomes and characterize the effects of ongoing disruptions.
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COVID-19 , Neoplasias Colorrectales , Centros de Atención Terciaria , Humanos , COVID-19/epidemiología , Masculino , Femenino , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Victoria/epidemiología , SARS-CoV-2 , Resultado del Tratamiento , Anciano de 80 o más Años , Adulto , PandemiasRESUMEN
Clonal hematopoiesis (CH) arises when a hematopoietic stem cell (HSC) acquires a mutation that confers a competitive advantage over wild-type (WT) HSCs, resulting in its clonal expansion. Individuals with CH are at an increased risk of developing hematologic neoplasms and a range of age-related inflammatory illnesses1-3. Therapeutic interventions that suppress the expansion of mutant HSCs have the potential to prevent these CH-related illnesses; however, such interventions have not yet been identified. The most common CH driver mutations are in the DNA methyltransferase 3 alpha (DNMT3A) gene with arginine 882 (R882) being a mutation hotspot. Here we show that murine hematopoietic stem and progenitor cells (HSPCs) carrying the Dnmt3aR878H/+ mutation, which is equivalent to human DNMT3AR882H/+, have increased mitochondrial respiration compared with WT cells and are dependent on this metabolic reprogramming for their competitive advantage. Importantly, treatment with metformin, an oral anti-diabetic drug with inhibitory activity against complex I in the electron transport chain (ETC), reduced the fitness of Dnmt3aR878H/+ HSCs. Through a multi-omics approach, we discovered that metformin acts by enhancing the methylation potential in Dnmt3aR878H/+ HSPCs and reversing their aberrant DNA CpG methylation and histone H3K27 trimethylation (H3K27me3) profiles. Metformin also reduced the fitness of human DNMT3AR882H HSPCs generated by prime editing. Our findings provide preclinical rationale for investigating metformin as a preventive intervention against illnesses associated with DNMT3AR882 mutation-driven CH in humans.
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ABSTRACT: Transformation of BCR::ABL1-negative myeloproliferative neoplasms (MPN) to an accelerated or blast phase is associated with poor outcomes. The efficacy of acute myeloid leukemia (AML)-type intensive and nonintensive hypomethylating agent-based regimens is not well studied. We therefore performed a retrospective analysis of patients with MPN-AP/BP (N = 138) treated with intensive (N = 81) and nonintensive (N = 57) blast-reduction strategies. We used clinically relatable response criteria developed at the Princess Margaret Cancer Centre. The overall best response, comprising complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and reversion to chronic phase MPN (cMPN), in the intensive and nonintensive groups was 77% (62 of 81) and 39% (21 of 54), respectively. Similar overall best response rates were observed in patients receiving induction with daunorubicin combined with cytarabine arabinoside (daunorubicin + ara-C) (74% [23 of 31]) or FLAG-IDA/NOVE-HiDAC (78% [39 of 50], P = .78). However, patients receiving daunorubicin + ara-C more often required second inductions (29% [9 of 31] vs 4% [2 of 50], P = .002). Most responses in the entire cohort were reversions to cMPN (55 of 83 [66%]). CR and CRi comprised 30% (25 of 83) and 4% (3 of 83) of responses, respectively. Mutations in TP53 (overall response [OR] 8.2 [95% confidence interval [CI] 2.01, 37.1], P = .004) and RAS pathway (OR 5.1 [95%CI 1.2, 23.7], P = .03) were associated with inferior treatment response for intensively treated patients, and poorer performance status (Eastern Cooperative Oncology Group) was associated with inferior treatment response in both intensively (OR 10.4 [95% CI 2.0, 78.5], P = .009) and nonintensively treated groups (OR 12 [95% CI 2.04, 230.3], P = .02). In patients with paired samples before and after therapy (N = 26), there was a significant residual mutation burden remaining irrespective of response to blast-reduction therapy.
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Trastornos Mieloproliferativos , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Trastornos Mieloproliferativos/genética , Citarabina/uso terapéutico , DaunorrubicinaRESUMEN
Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRDpos) post-induction. MRDpos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRDneg patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRDpos patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRDpos intermediate-risk AML patients.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Citometría de Flujo , Estudios Retrospectivos , Trasplante Homólogo , Recurrencia , Neoplasia Residual , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , PronósticoRESUMEN
Background: Asynchronous telepsychiatry (ATP) consultations are a novel form of psychiatric consultation. Studies comparing patient and provider satisfaction for ATP with that for synchronous telepsychiatry (STP) do not exist. Methods: This mixed-methods study is a secondary analysis of patients' and primary care providers' (PCPs) satisfaction from a randomized clinical trial of ATP compared with STP. Patients and their PCPs completed satisfaction surveys, and provided unstructured feedback about their experiences with either ATP or STP. Differences in patient satisfaction were assessed using mixed-effects logistic regression models, and the qualitative data were analyzed using thematic analysis with an inductive coding framework. Results: Patient satisfaction overall was high with 84% and 97% of respondents at 6 months reported being somewhat or completely satisfied with ATP and STP, respectively. Patients in the STP group were more likely to report being completely satisfied, to recommend the program to a friend, and to report being comfortable with their care compared with ATP (all p < 0.05). However, there was no difference between the patients in ATP and STP in perceived change in clinical outcomes (p = 0.51). The PCP quantitative data were small, and thus only summarized descriptively. Conclusions: Patients expressed their overall satisfaction with both STP and ATP. Patients in ATP reported more concerns about the process, likely because feedback after ATP was slower than that after STP consultations. PCPs had no apparent preference for STP or ATP, and reported implementing the psychiatrists' recommendations for both groups when such recommendations were made, which supports our previous findings. Trial Registration: ClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979.
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Psiquiatría , Telemedicina , Humanos , Satisfacción del Paciente , Satisfacción Personal , Atención Primaria de Salud , Adenosina TrifosfatoRESUMEN
BACKGROUND: In recent years, certain body composition measures, assessed by computed tomography (CT), have been found to be associated with chemotherapy toxicities. This review aims to explore available data on the relationship between skeletal muscle and adiposity, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intramuscular and intermuscular adipose tissue and their association with chemotherapy toxicity in non-metastatic colorectal cancer (CRC) patients. METHODS: A systematic literature search following PRISMA guidelines was conducted in Medline, Embase, Cochrane and Web of Science, for papers published between 2011 and 2023. The search strategy combined keywords and MESH terms relevant to 'body composition', 'chemotherapy toxicities', and 'non-metastatic colorectal cancer'. RESULTS: Out of 3868 studies identified, six retrospective studies fulfilled the inclusion criteria with 1024 eligible patients. Low skeletal muscle mass was strongly associated with increased incidence of both chemotherapy toxicities and dose-limiting toxicity (DLT). The association of VAT, intramuscular and intermuscular adiposity was heterogeneous and inconclusive. There was no association between SAT and chemotherapy intolerance. No universal definitions or cut-offs for sarcopenia and obesity were noted. All studies utilized 2-dimensional (2D) CT slices for CT body composition assessment with varied selection on the vertebral landmark and inconsistent reporting of tissue-defining Hounsfield unit (HU) measurements. CONCLUSION: Low skeletal muscle is associated with chemotherapy toxicities in non-metastatic CRC. However, quality evidence on the role of adiposity is limited and heterogeneous. More studies are needed to confirm these associations with an emphasis on a more coherent body composition definition and an approach to its assessment, especially regarding sarcopenia.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Sarcopenia , Humanos , Sarcopenia/inducido químicamente , Sarcopenia/diagnóstico por imagen , Sarcopenia/complicaciones , Estudios Retrospectivos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Composición Corporal/fisiología , Obesidad/complicaciones , Neoplasias del Colon/patología , Neoplasias del Recto/patología , Neoplasias Colorrectales/patologíaAsunto(s)
Isocitrato Deshidrogenasa , Leucemia Mieloide Aguda , Humanos , Pronóstico , Factores de Empalme de ARN/genética , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutación , Neoplasia Residual/diagnóstico , Neoplasia Residual/genéticaRESUMEN
CFI-400945 is a selective oral polo-like kinase 4 (PLK4) inhibitor that regulates centriole duplication. PLK4 is aberrantly expressed in patients with acute myeloid leukemia (AML). Preclinical studies indicate that CFI-400945 has potent in vivo efficacy in hematological malignancies and xenograft models, with activity in cells harboring TP53 mutations. In this phase 1 study in very high-risk patients with relapsed/refractory AML and myelodysplastic syndrome (MDS) (NCT03187288), 13 patients were treated with CFI-400945 continuously in dose escalation from 64 mg/day to 128 mg/day. Three of the 9 efficacy evaluable AML patients achieved complete remission (CR). Two of 4 AML patients (50%) with TP53 mutations and complex monosomal karyotype achieved a CR with 1 patient proceeding to allogenic stem cell transplant. A third patient with TP53 mutated AML had a significant reduction in marrow blasts by > 50% with an improvement in neutrophil and platelet counts. Responses were observed after 1 cycle of therapy. Dose-limiting toxicity was enteritis/colitis. A monotherapy and combination therapy study with a newer crystal form of CFI-400945 in patients with AML, MDS and chronic myelomonocytic leukemia (CMML) is ongoing (NCT04730258).
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Indazoles , Indoles , Leucemia Mieloide Aguda , Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Humanos , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicos/genética , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Supervivencia sin Enfermedad , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
PURPOSE: Gold standard chemotherapy dosage is based on body surface area (BSA); however many patients experience dose-limiting toxicities (DLT). We aimed to evaluate the effectiveness of BSA, two-dimensional (2D) and three-dimensional (3D) body composition (BC) measurements derived from Lumbar 3 vertebra (L3) computed tomography (CT) slices, in predicting DLT in colon cancer patients. METHODS: 203 patients (60.87 ± 12.42 years; 97 males, 47.8%) receiving adjuvant chemotherapy (Oxaliplatin and/or 5-Fluorouracil) were retrospectively evaluated. An artificial intelligence segmentation model was used to extract 2D and 3D body composition measurements from each patients' single mid-L3 CT slice as well as multiple-L3 CT scans to produce a 3D BC report. DLT was defined as any incidence of dose reduction or discontinuation due to chemotherapy toxicities. A receiver operating characteristic (ROC) analysis was performed on BSA and individual body composition measurements to demonstrate their predictive performance. RESULTS: A total of 120 (59.1%) patients experienced DLT. Age and BSA did not vary significantly between DLT and non-DLT group. Females were significantly more likely to experience DLT (p = 4.9 × 10-3). In all patients, the predictive effectiveness of 2D body composition measurements (females: AUC = 0.50-0.54; males: AUC = 0.50-0.61) was equivalent to that of BSA (females: AUC = 0.49; males: AUC = 0.58). The L3 3D skeletal muscle volume was the most predictive indicator of DLT (AUC of 0.66 in females and 0.64 in males). CONCLUSION: Compared to BSA and 2D body composition measurements, 3D L3 body composition measurements had greater potential to predict DLT in CRC patients receiving chemotherapy and this was sex dependent.
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Purpose of review: Patients, providers, and trainees should understand the current types of asynchronous technologies that can be used to enhance the delivery and accessibility of mental health care. Asynchronous telepsychiatry (ATP) removes the need for real time communication between the clinician and patient, which improves efficiency and enables quality specialty care. ATP can be applied as distinct consultative and supervisory models in clinician-to-clinician, clinician-to-patient, and patient-to-mobile health settings. Recent findings: This review is based on research literature and the authors' clinical and medical training, using experiences with asynchronous telepsychiatry from before, during, and after the COVID-19 pandemic. Our studies demonstrate that ATP provides positive outcomes in the clinician-to-patient model with demonstrated feasibility, outcomes and patient satisfaction. One author's medical education experience in the Philippines during COVID-19 highlights the potential to utilize asynchronous technology in areas with limitations to online learning. We emphasize the need to teach media skills literacy around mental health to students, coaches, therapists, and clinicians when advocating for mental well-being. Several studies have demonstrated the feasibility of incorporating asynchronous e-tools such as self-guided multimedia and artificial intelligence for data collection at the clinician-to-clinician and patient-to-mobile health level. In addition, we offer fresh perspectives on recent trends in asynchronous telehealth in wellness, applying concepts such as "tele-exercise" and "tele-yoga." Summary: Asynchronous technologies continue to be integrated into mental health care services and research. Future research must ensure that the design and the usability of this technology puts the patient and provider first.
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INTRODUCTION: Care for patients with acute myeloid leukemia (AML) is centralized in the Ontario single-payer public healthcare system, with intensive induction chemotherapy and clinical trials only offered at specialized cancer centers with large catchment areas. METHODS: We therefore conducted a retrospective single-center review of all AML patients assessed at a large specialized cancer center in Ontario, Canada. RESULTS: Between 2012 and 2017, 1,310 patients were assessed by our center for upfront AML therapy. The median distance was 33.1 km, with 29% of patients living more than 50 km away from the center. There was no significant difference in probability of intensive induction chemotherapy or clinical trial by distance from center, both in univariate and multivariable analysis adjusting for age, sex, cytogenetics and molecular testing, and performance status. There was no significant difference in overall survival by distance from center on univariate and multivariable analysis. CONCLUSION: In conclusion, geographic distance from treatment center does not appear to impact choice of upfront therapy, participation in clinical trials, or clinical outcomes in this study of newly diagnosed patients with AML treated in a single-payer environment.
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Quimioterapia de Inducción , Leucemia Mieloide Aguda , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: There is mounting evidence that suggests sarcopenia can be used to predict survival outcomes in patients with colon cancer. However, the effect on locally advanced rectal cancer (LARC) is less clear. We sought to determine the association between sarcopenia on Overall Survival and Recurrence-free Survival (OS and RFS) in patients with LARC undergoing multimodal treatment. METHODS: A retrospective study was undertaken of all pre-treatment stage 2-3 rectal cancer patients who underwent neo-adjuvant treatment and surgery with curative intent between January 2010 and September 2016 at Western Health. Sarcopenia was measured on pre-treatment staging scans at the third lumbar vertebrae and defined using cohort-derived, sex-specific thresholds. Primary outcomes were OS and RFS. RESULTS: A total of 132 patients with LARC were analysed. Sarcopenia: Hazard ratio (HR) 3.71; 95% CI, 1.28-10.75, P = 0.016 was independently associated with worse Overall Survival following multivariate analysis. There was no significant relationship between sarcopenia and RFS: Time ratio (TR) 1.67; 95% CI 0.52-5.34, P = 0.386. CONCLUSION: Sarcopenia was found to be an independent risk factor for worse overall survival, but not recurrence free survival, in patients with locally advanced rectal cancer undergoing neo-adjuvant chemo-radiotherapy and surgery with curative intent.
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Neoplasias del Recto , Sarcopenia , Masculino , Femenino , Humanos , Sarcopenia/complicaciones , Estudios Retrospectivos , Neoplasias del Recto/terapia , Neoplasias del Recto/tratamiento farmacológico , Quimioterapia Adyuvante/efectos adversos , Terapia Combinada , Pronóstico , Terapia Neoadyuvante/efectos adversosRESUMEN
Venetoclax requires a 75% dose reduction when coadministered with voriconazole. In a 10-year historical cohort of treatment with venetoclax, we did not observe a worse hematologic outcome in patients who received voriconazole prophylaxis versus those who did not. Subtherapeutic voriconazole levels and a triazole exposure history may contribute to breakthrough invasive fungal infection.
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BACKGROUND: Inconclusive cytogenetic analysis (IC) at baseline has been reported as a predictor of poor prognosis in patients with acute myeloid leukemia (AML). The mutational profile in this group of patients, and its impact on outcomes have not been reported. METHODS: We retrospectively analyzed adult patients (≥18 years) with newly diagnosed AML treated with intensive induction chemotherapy between 2015 and 2019. Patients with any documented cytogenetic abnormalities were excluded. Targeted next generation sequencing (NGS) was performed in all patients. Baseline characteristics, mutation profile, and outcomes were compared between patients with normal cytogenetics(NC) and those with IC. RESULTS: Sixty-one patients (males 39.3%; median age 59 years) had IC at diagnosis. The proportion of patients with mutations in genes with proven prognostic impact were not different between AML patients with IC and NC. AML patients with NC were more likely to harbor the prognostically favorable NPM1mut /FLT3-ITDwt mutational combination conferring "favorable" risk status. As a result, a larger proportion of patients in the IC group underwent allogeneic hematopoietic stem cell transplantation (allo HCT; 54.1% vs. 39.6%; p = .02). The 2-year RFS (55.9% vs. 58.5%; p = .29) and OS (61.9% vs. 66.9%; p = .48) were similar in IC and NC patients. There was no difference in survival of patients who underwent allo HCT when compared with patients who did not (p = .99). CONCLUSIONS: Inconclusive cytogenetic analysis may not be an independent prognostic indicator in AML. In such patients, molecular abnormalities detected through NGS or whole genome sequencing are more likely to be informative.