RESUMEN
Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.
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Anticuerpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Inducción , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Adulto Joven , Quimioterapia de Inducción/métodos , Anciano , Adolescente , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos , Inducción de RemisiónRESUMEN
BACKGROUND: A standardised dose-reduction strategy has not been established for the widely used gemcitabine plus nab-paclitaxel regimen in patients with metastatic pancreatic ductal adenocarcinoma. We aimed to investigate the efficacy and tolerability of alternating treatment cycles of nab-paclitaxel-gemcitabine combination therapy and gemcitabine alone versus continuous treatment with the nab-paclitaxel-gemcitabine combination. METHODS: ALPACA was a randomised, open-label, phase 2 trial conducted at 29 study centres across Germany. Patients aged 18 years or older with a histologically or cytologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma who had not been previously treated for advanced disease were enrolled. After an induction phase with three cycles of nab-paclitaxel-gemcitabine combination therapy (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 administered intravenously on days 1, 8, and 15 of each 28-day cycle), patients were randomly assigned (1:1) by stratified permuted block randomisation either to continue treatment with standard nab-paclitaxel-gemcitabine or to receive alternating cycles of nab-paclitaxel-gemcitabine and gemcitabine alone. Patients and investigators were not masked to treatment allocation. Randomisation was done centrally by the study statistician using a computer-generated randomisation list, and was stratified by Karnofsky Performance Status and presence of liver metastases. The primary endpoint was the derivation of an unbiased point estimate and an associated confidence interval with a confidence coefficient of 80% for the hazard ratio (HR) for overall survival after randomisation, without testing a specific hypothesis, analysed by intention to treat in all patients who started randomised treatment. Safety was analysed according to treatment received. This trial is registered with ClinicalTrials.gov, NCT02564146, and is completed. FINDINGS: Between May 27, 2016, and May 27, 2021, 325 patients were enrolled. Following three cycles of induction treatment, 174 patients were randomly assigned: 85 to continue receiving standard nab-paclitaxel-gemcitabine, of whom 79 started treatment, and 89 to the alternating treatment schedule, of whom 88 started treatment. Of the 167 patients who started randomised treatment, 88 (53%) were female and 79 (47%) were male. Median overall survival after randomisation was 10·4 months (80% CI 9·2-12·0) in the group that received standard treatment and 10·5 months (10·2-11·1) in the group that received alternating treatment (HR 0·90, 80% CI 0·72-1·13; p=0·56). The most common adverse events of any grade were peripheral neuropathy (59 [74%] of 80 patients in the continuous treatment group vs 53 [62%] of 85 patients in the alternating treatment group) and fatigue (43 [54%] vs 44 [52%]). Treatment-emergent serious adverse events after randomisation occurred in 40 (50%) patients in the continuous treatment group and in 28 (33%) in the alternating treatment group. Fewer treatment-emergent adverse events of grade 3 or higher occurred in patients treated with alternating cycles compared with those receiving standard therapy, especially for peripheral neuropathy (17 [21%] patients in the continuous treatment group vs 12 [14%] in the alternating treatment group) and infections (16 [20%] vs nine [11%]). There were two treatment-related deaths after randomisation, both in the continuous treatment group (one multiple organ dysfunction syndrome, not treated after randomisation, and one interstitial lung disease). INTERPRETATION: Our findings suggest that a dose-reduced regimen with alternating cycles of nab-paclitaxel-gemcitabine and gemcitabine alone after three induction cycles is associated with similar overall survival to that for standard treatment with nab-paclitaxel-gemcitabine, but with improved tolerability. We therefore propose that a switch to the alternating schedule could be considered in a clinical setting for patients with metastatic pancreatic cancer who have at least stable disease after three cycles of nab-paclitaxel-gemcitabine treatment. FUNDING: Celgene/Bristol Myers Squibb.
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Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático , Desoxicitidina , Gemcitabina , Paclitaxel , Neoplasias Pancreáticas , Humanos , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Desoxicitidina/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Quimioterapia de Inducción/métodos , Esquema de MedicaciónRESUMEN
PURPOSE: To establish and validate a delta-radiomics-based model for predicting progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) following induction chemotherapy (IC). METHODS AND MATERIALS: A total of 250 LA-NPC patients (training cohort: n = 145; validation cohort: n = 105) were enrolled. Radiomic features were extracted from MRI scans taken before and after IC, and changes in these features were calculated. Following feature selection, a delta-radiomics signature was constructed using LASSO-Cox regression analysis. A prognostic nomogram incorporating independent clinical indicators and the delta-radiomics signature was developed and assessed for calibration and discrimination. Risk stratification by the nomogram was evaluated using Kaplan-Meier methods. RESULTS: The delta-radiomics signature, consisting of 12 features, was independently associated with prognosis. The nomogram, integrating the delta-radiomics signature and clinical factors demonstrated excellent calibration and discrimination. The model achieved a Harrell's concordance index (C-index) of 0.848 in the training cohort and 0.820 in the validation cohort. Risk stratification identified two groups with significantly different PFS rates. The three-year PFS for high-risk patients who received concurrent chemoradiotherapy (CCRT) or radiotherapy plus adjuvant chemotherapy (RT+AC) after IC was significantly higher than for those who received RT alone, reaching statistical significance. In contrast, for low-risk patients, the three-year PFS after IC was slightly higher for those who received CCRT or RT+AC compared to those who received RT alone; however, this difference did not reach statistical significance. CONCLUSIONS: Our delta MRI-based radiomics model could be useful for predicting PFS and may guide subsequent treatment decisions after IC in LA-NPC.
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Quimioterapia de Inducción , Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Radiómica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quimioterapia de Inducción/métodos , Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/radioterapia , Pronóstico , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. METHODS: We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. RESULTS: Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. CONCLUSIONS: This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.
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Anticuerpos Monoclonales Humanizados , Quimioradioterapia , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Quimioradioterapia/métodos , Quimioterapia de Inducción/métodos , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Estudios Retrospectivos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Adulto , Anciano , Estadificación de Neoplasias , Resultado del Tratamiento , Estimación de Kaplan-Meier , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Adulto JovenRESUMEN
The research paper offers a detailed analysis of induction chemotherapy regimens for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), assessing their effectiveness and cost-effectiveness. It presents important data on disease-free survival and overall survival outcomes. However, this letter suggests several improvements. It advocates for the inclusion of patient-centered outcomes such as quality of life and functional status to better gauge treatment impacts on daily living. Additionally, it calls for a more thorough investigation into long-term adverse effects and the role of biomarkers in tailoring treatments. It also recommends a comparative analysis of cost-effectiveness across various healthcare systems and the creation of practical guidelines for regimen selection. These proposed changes aim to enhance the study's practical relevance and clinical applicability.
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Análisis de Costo-Efectividad , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Quimioterapia de Inducción/economía , Quimioterapia de Inducción/métodos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/economía , Neoplasias Nasofaríngeas/patología , Metaanálisis en Red , Calidad de VidaRESUMEN
The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.
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Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia de Inducción/métodos , Femenino , Masculino , Persona de Mediana Edad , AdultoRESUMEN
BACKGROUND: Lung cancer is associated with a high mortality rate worldwide. Non-small-cell lung cancer (NSCLC) is a major subtype of lung cancer. Carboplatin (CBDCA) plus nab-paclitaxel (PTX) has become a standard treatment for advanced unresectable NSCLC. However, treatment with nab-PTX has not been established as a standard therapy for resectable locally advanced (LA)-NSCLC. METHODS: We conducted a comprehensive study involving consecutive patients with locally advanced NSCLC who underwent induction therapy including nab-PTX followed by surgical resection. Fifteen patients with locally advanced NSCLC underwent induction therapy including nab-PTX followed by surgical resection. Concurrent chemoradiotherapy (CRT) consisted of weekly administration of nab-PTX (50 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (50 Gy/25 fractions). RESULTS: The clinical stages were as follows: IIB (n =1), IIIA (n =12), and IIIC (n =2). Downstaging was observed in 73% (11/15) of patients on comparison with the clinical stage before concurrent CRT. Adverse drug reactions were observed in seven patients. Complete resection was performed in all patients. The re-evaluated pathological stage after pretreatment was diagnosed as stage 0 in three patients, stage IA1 in six, stage IA2 in one, and stage IIIA in five. The pathological effects of previous therapy were as follows: Ef3 (n =3), Ef2 (n =9), and Ef1a (n =3). CONCLUSION: The therapeutic effect of induction therapy including nab-PTX was promising. Induction CRT, including nab-PTX, followed by resection, may be a viable alternative treatment option for locally advanced NSCLC.
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Albúminas , Carcinoma de Pulmón de Células no Pequeñas , Quimioterapia de Inducción , Neoplasias Pulmonares , Paclitaxel , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Femenino , Albúminas/uso terapéutico , Albúminas/administración & dosificación , Persona de Mediana Edad , Anciano , Quimioterapia de Inducción/métodos , Estadificación de Neoplasias , Neumonectomía/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim is to identify preventable cause for hospital readmissions during induction and implement interventions to decreased preventable treatment-associated complications. BACKGROUND: Multiple factors contribute to patients with acute lymphoblastic leukemia (ALL) requiring readmissions during induction. MATERIALS AND METHODS: A dashboard monitored features of newly diagnosed patients with ALL. Readmission causes were stratified as preventable, possibly preventable, or unpreventable. A discharge checklist, including standardized education, and change of discharge date were implemented. RESULTS: Initially, there were 57 hospital readmissions of 98 patients (9 intensive care unit admissions and 2 deaths). Sixteen preventable (28.1%) and 32 unpreventable (56.1%) readmissions. After the interventions were initiated, including improved education, discharge checklist utilization, and standardized discharge date, there were 23 readmissions (78.3% were unpreventable, 6 intensive care unit admissions). CONCLUSION: Intervention implementation reduced readmission rates of induction patients with ALL by 20%.
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Lista de Verificación , Alta del Paciente , Readmisión del Paciente , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Readmisión del Paciente/estadística & datos numéricos , Niño , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Masculino , Femenino , Preescolar , Adolescente , Educación del Paciente como Asunto/métodos , Lactante , Quimioterapia de Inducción/métodosRESUMEN
BACKGROUND: Total neoadjuvant therapy (TNT) before surgical intervention represents a unique therapeutic approach for the management of locally advanced rectal cancer (LARC) and has witnessed a notable rise in utilization within recent years. However, the efficacy and safety of this treatment remain subjects of ongoing debate and investigation. This randomized controlled trial aimed to evaluate the potential impact of administering induction chemotherapy (IC) before the conventional neoadjuvant concomitant chemoradiotherapy (nCRT) in LARC patients. MATERIALS & METHODS: patients with resectable stage II-III LARC were randomly allocated to receive either biweekly 6 cycles of FOLFOX4 regimen as IC followed by CRT and total mesorectal excision (TME) (experimental group) or nCRT followed by TME (control group). The primary endpoint was the rate of pathological complete response (pCR). The secondary endpoints encompassed the evaluation of treatment-related adverse events as well as the assessment of survival outcomes. RESULTS: 67 patients were enrolled in this study (32 in the experimental group and 35 in the control group). The median age of the patients was 45 years. Stage IIIB was observed in 46.3% of the patients. The patients who underwent induction chemotherapy demonstrated a notably higher rate of achieving pCR in comparison to the control group (28.1% vs 8.6%; P=0.001). There were no statistically significant differences observed in terms of their toxicity profile and survival outcomes. CONCLUSIONS: Implementation of induction chemotherapy utilizing the FOLFOX4 regimen has demonstrated a notable enhancement in the rate of pathological complete response. However, this improvement does not appear to translate into significant advancements in overall survival outcomes.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Leucovorina , Terapia Neoadyuvante , Compuestos Organoplatinos , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/tratamiento farmacológico , Femenino , Masculino , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Adulto , Tasa de Supervivencia , Pronóstico , Estudios de Seguimiento , Quimioradioterapia/métodos , Anciano , Quimioterapia Adyuvante/métodos , Quimioterapia de Inducción/métodos , Cuidados PreoperatoriosRESUMEN
BACKGROUND: Maintenance therapy could significantly improve the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. Anlotinib is effective, tolerable, and convenient in administration as a third-line treatment for NSCLC. This study aimed to evaluate the efficacy and safety of maintenance therapy with anlotinib after platinum-based induction chemotherapy for patients with advanced NSCLC. METHODS: This pooled analysis of 2 multicenter, open-label, single-arm, phase 2 clinical trials (ALTER-L014 and ALTER-L011) enrolled patients with locally advanced or metastatic NSCLC and without known sensitive mutations in China between September 2018 and January 2021. The primary outcome was progression-free survival. The secondary outcomes were objective response rate, disease control rate, overall survival, and safety. RESULTS: The data of 23 patients were pooled, with 15 from ALTER-L014 and 8 from ALTER-L011. At the cutoff date of June 13, 2021, the median progression-free survival since the start of maintenance therapy was 5.95 (95% confidence interval, 4.30-8.80) months. Nineteen patients had stable disease, 1 had a partial response and 3 had progressive disease. The objective response rate was 4.35%, while disease control rate was 86.96%. The median overall survival of the patients since the start of maintenance therapy was 18.60 (95% confidence interval, 6.87-22.80) months. The incidence of adverse events of gradeâ ≥â 3 was 21.7%. CONCLUSION: Anlotinib might offer a new option for maintenance treatment in patients with locally advanced or metastatic NSCLC without known sensitive mutations after standard first-line platinum-based chemotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Indoles , Quimioterapia de Inducción , Neoplasias Pulmonares , Quinolinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Indoles/uso terapéutico , Indoles/administración & dosificación , Indoles/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Femenino , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Anciano , Quimioterapia de Inducción/métodos , Quimioterapia de Mantención/métodos , Adulto , Supervivencia sin Progresión , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare disease worldwide; To the best of our knowledge, there is no established standard of care specifically tailored for the adolescent population. The majority of existing research relies on retrospective data analysis. OBJECTIVE: Evaluate clinical features, treatment results, prognostic factors and late toxicities of locally advanced NPC patients treated with tomotherapy. DESIGN: Retrospective. SETTINGS: Tertiary care hospital. PATIENTS AND METHODS: Between January 2007 and January 2020, we treated patients with NPC, aged between 14 and 21 years, with concomitant chemoradiotherapy using tomotherapy at our institution. We prospectively collected details of clinical characteristics, treatment modalities, outcomes and prognostic factors of these patients and then analysed them retrospectively. MAIN OUTCOME MEASURES: 3-5 years overall survival (OS), 3-5 years locoregional control rate, 3-5 years disease-free survival (DFS), prognostic factors. SAMPLE SIZE: 51 patients. RESULTS: There were 26 male and 25 female patients included in our study. The mean age was 16.5 years, 5 (9.8%) patients with stage III, and 46 (90.2%) with stage IVa according to the American Joint Committee on Cancer, 8th edition staging system. Most patients (98%) received two or more cycles of induction chemotherapy. All patients received concomitant chemoradiotherapy. The median total dose of radiotherapy delivered was 6600 cGy (range 4800-7000). With a median follow-up of 73 months (range 9-168 months), a 5-year locoregional control rate, 5-year OS and 5-year DFS rates were 100%, 86.8% and 71.7%, respectively. Five years later, disease control was 71.7%. Ten (19.6%) patients had disease recurrence in the form of distant metastases during the follow up. CONCLUSIONS: Helical tomotherapy has an excellent late toxicity profile without compromising clinical outcome for patients with NPC. Radiotherapy remains the mainstay of treatment of nasopharyngeal carcinoma to achieve remarkable local control rates. LIMITATIONS: Single institution experience, small number of patients, and retrospective design.
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Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadificación de Neoplasias , Radioterapia de Intensidad Modulada , Humanos , Femenino , Masculino , Adolescente , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patología , Estudios Retrospectivos , Radioterapia de Intensidad Modulada/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Adulto Joven , Quimioradioterapia/métodos , Supervivencia sin Enfermedad , Arabia Saudita , Pronóstico , Resultado del Tratamiento , Tasa de Supervivencia , Quimioterapia de Inducción/métodosRESUMEN
OBJECTIVE: The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. PATIENTS AND METHODS: We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. RESULTS: According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. CONCLUSION: Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.
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Análisis Costo-Beneficio , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Metaanálisis en Red , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/economía , Carcinoma Nasofaríngeo/mortalidad , Quimioterapia de Inducción/economía , Quimioterapia de Inducción/métodos , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/economía , Años de Vida Ajustados por Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Análisis de Costo-EfectividadRESUMEN
PURPOSE: Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes. METHODS: We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. RESULTS: Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations. CONCLUSIONS: In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs.
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Suero Antilinfocítico , Rechazo de Injerto , Supervivencia de Injerto , Infecciones por VIH , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Adulto , Persona de Mediana Edad , Suero Antilinfocítico/uso terapéutico , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Antirretrovirales/uso terapéutico , Quimioterapia de Inducción/métodos , Receptores de Trasplantes/estadística & datos numéricos , Resultado del Tratamiento , Terapia de Inmunosupresión/métodosRESUMEN
OBJECTIVES: Mycophenolic acid (MPA) is recommended for lupus nephritis (LN) treatment, but with large inter-individual variability in pharmacokinetics (PK). The aim of this study is to reveal the relationship between MPA exposure and disease response and adverse drug reactions in pediatric LN patients. METHOD: This was a population-based observational cohort study. A total of 86 pediatric LN patients treated with mycophenolate mofetil (MMF) for induction therapy were enrolled. The area-under the concentration-time curve (AUC) was calculated using MPA concentrations according to a limited sampling strategy. Receiver operating characteristic analysis was performed to assess the MPA-AUC threshold values. The cumulative incidence of renal remission and inactive systemic lupus erythematosus (SLE) over time was evaluated by Kaplan-Meier's analysis. RESULTS: MPA-AUC was identified as an independent factor associated with renal remission and lupus activity at 6 and 12 months after MMF treatment, and the improved renal remission rates were correlated with higher MPA-AUC, with thresholds of 29.81 and 30.63 µg·h·mL-1 at 6 months and 12 months, respectively. Furthermore, the thresholds for maintaining the hypoactive state of LN were 30.96 and 31.19 µg·h·mL-1at 6 months and 12 months, respectively. Patients reaching target thresholds for MPA-AUC achieved renal response or stable disease earlier. In addition, the MPA-AUC threshold for decreasing MMF-related adverse reactions was 50.80 µg·h·mL-1. CONCLUSION: The initial and long-term treatments of pediatric LN patients with MMF should be individualized according to the MPA-AUC, and the recommended MPA exposure is 31.19-50.80 µg·h·mL-1.
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Inmunosupresores , Nefritis Lúpica , Ácido Micofenólico , Inducción de Remisión , Humanos , Nefritis Lúpica/tratamiento farmacológico , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/farmacocinética , Femenino , Masculino , Niño , Inmunosupresores/uso terapéutico , Inmunosupresores/farmacocinética , Inmunosupresores/efectos adversos , Adolescente , Estudios de Cohortes , Área Bajo la Curva , Quimioterapia de Inducción/métodos , Resultado del TratamientoRESUMEN
Predictors for response to intensive therapy in AML have focused on baseline factors: percent leukemic blasts in marrow, cytogenetic/molecular genetic abnormalities, and presence of secondary AML. Non-baseline dynamic factors, occurring after induction but before response, may be useful for decisions related to salvage chemotherapy. We hypothesized white blood cell (WBC) count nadir after induction may be a real time indicator of treatment efficacy. We also examined whether time to stem cell transplant (SCT) or baseline molecular genetic abnormalities are associated with a low nadir. Data showed WBC nadir = 0 was a negative predictor for response to intensive induction and was correlated with reduced overall survival and progression free survival. Patients with WBC nadir = 0 did not have a significantly longer time to SCT, and none of the mutations increased the likelihood of reaching WBC nadir = 0. WBC nadir may be a useful real-time monitor in AML patients receiving intensive induction chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/genética , Recuento de Leucocitos , Persona de Mediana Edad , Masculino , Femenino , Pronóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Quimioterapia de Inducción/métodos , Resultado del Tratamiento , Adulto Joven , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
OBJECTIVES: To determine the outcomes for elderly patients with de novo metastatic germ cell tumors and the influence of patient age on adherence to standard chemotherapy. METHODS: A total of 150 patients who were initially diagnosed with metastatic germ cell tumors and treated at our institution between 2007 and 2021 were included. Patients were classified according to three age groups: aged <40, 40-49, and ≥50 years. Clinicopathological features, adherence to standard first-line chemotherapy, overall survival, and disease-free survival were compared between these groups. We also analyzed the outcomes of patients who received low-intensity induction chemotherapy due to adverse events and/or comorbidities. RESULTS: There was no significant difference in any of the survival outcomes and in the rate of adherence to standard first-line chemotherapy between the three age groups, although elderly patients with intermediate/poor prognosis group tended to receive less-intense chemotherapies. The rate of febrile neutropenia as a chemotherapy-related adverse event was significantly higher in patients aged ≥50 years. No statistical significance in survival outcomes was detected between the group of patients who received relatively low-intensity induction chemotherapy and those who received adequately intensive planned chemotherapy. CONCLUSIONS: The adherence rate of standard fist-line chemotherapy of elderly patients is almost comparable to that of younger patients, although some adverse events should be carefully managed. Even elderly patients with metastatic germ cell tumors can aim for equivalently good survival outcome like younger populations, with effort to adhere to standard chemotherapy.
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Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/secundario , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias de Células Germinales y Embrionarias/patología , Persona de Mediana Edad , Adulto , Factores de Edad , Estudios Retrospectivos , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/patología , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/terapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Quimioterapia de Inducción/métodos , Metástasis de la Neoplasia , Pronóstico , Adulto JovenRESUMEN
BACKGROUND: Thalidomide-containing regimens cause adverse events (AEs) that may require a reduction in treatment intensity or even treatment discontinuation in patients with multiple myeloma. As thalidomide toxicity is dose-dependent, identifying the most appropriate dose for each patient is essential. AIMS: This study aimed to investigate the effects of a thalidomide dose step-up strategy on treatment response and progression-free survival (PFS). METHODS AND RESULTS: This prospective observational study included 93 patients with newly diagnosed multiple myeloma (NDMM) who received bortezomib, thalidomide, and dexamethasone (VTD). The present study assessed the incidence of thalidomide dose reduction and discontinuation, the overall dose intensity, and their effects on therapeutic efficacy. Furthermore, this study used Cox proportional hazard models to analyze the factors contributing to thalidomide intolerability. The results showed the overall response rates in all patients and the evaluable patients were 78.5% and 98.7%, respectively. The median PFS in the study cohort was not reached. The most common thalidomide-related AEs were constipation (32.3%) and skin rash (23.7%), resulting in dose reduction and discontinuation rates of 22.6% and 21.5%, respectively. The responders had a significantly higher average thalidomide dose intensity than the nonresponders (88.6% vs. 42.9%, p < .001). CONCLUSION: The thalidomide dose step-up approach is a viable option for patients with NDMM receiving VTD induction therapy with satisfactory efficacy and tolerability. However, thalidomide intolerance may lead to dose reduction or discontinuation due to unpredictable AEs, leading to lower dose intensity and potentially inferior treatment outcomes. In addition to a dose step-up strategy, optimal supportive care is critical for patients with multiple myeloma receiving VTD induction therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Mieloma Múltiple , Talidomida , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/patología , Talidomida/administración & dosificación , Talidomida/efectos adversos , Femenino , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Masculino , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Quimioterapia de Inducción/métodos , Quimioterapia de Inducción/efectos adversos , Supervivencia sin Progresión , Anciano de 80 o más Años , Relación Dosis-Respuesta a DrogaRESUMEN
BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC
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Quimioradioterapia , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Puntaje de Propensión , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Persona de Mediana Edad , Quimioradioterapia/métodos , Adulto , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/tratamiento farmacológico , Quimioterapia de Inducción/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Anciano , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Estudios Retrospectivos , GemcitabinaRESUMEN
Objectives: To compare the efficacy of mycophenolate mofetil with intravenous cyclophosphamideas induction therapy in lupus nephritis. METHODS: The observational, prospecrive, cohort study was conducted at the Rheumatology Department of Fatima Memorial Hospital, Lahore, Pakistan, from July 2016 to June 2019, and comprised lupus nephritis patients. For induction therapy, the patients were assigned at the discretion of the treating rheumatologist to mycophenolate mofetil group MMF, and intravenous cyclophosphamide group CYC. The latter group was further divided into NIH subgroup that received the therapy as per the protocol of the National Institutes of Health, and ELNT subgroup which recived the therapy as per the Euro Lupus Nephritis Trial protocol. Maintenance therapy in all groups was mycophenolate mofetil. Tacrolimus was added in case of non-response. The outcome was the achievement of complete renal response at 6, 12 and 24 months. Data was analysed using SPSS 26. RESULTS: Of the 131 patients, 126(96.2%) were females. The overall mean age was 27±7.7 years. There were 58(44.2%) patients in group MMF and 73(55.7%) in group CYC, which had subgroup NIH 46(63%) and subgrpup ELNT 27(37%). The complete renal response rates at 6, 12, and 24 months were 22 (43.1%), 35 (71.4%), and 40(83.3%) for group MMF; 5(12.5%), 9(22%) and 24 (58.5%) for subgroup NIH, and 6(26.1%), 8(36.4%) and 14(63.6%) for subgroup ELNT. Group MMF outcomes were significantly better than the rest (p<0.05). CONCLUSIONS: Mycophenolate mofetil induction therapy was more effective than intraveenous cyclophosphamide in terms of achieving remission at 6, 12 and 24 months.
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Ciclofosfamida , Inmunosupresores , Nefritis Lúpica , Ácido Micofenólico , Centros de Atención Terciaria , Humanos , Nefritis Lúpica/tratamiento farmacológico , Ácido Micofenólico/uso terapéutico , Ciclofosfamida/uso terapéutico , Femenino , Adulto , Pakistán , Masculino , Inmunosupresores/uso terapéutico , Adulto Joven , Resultado del Tratamiento , Estudios de Cohortes , Tacrolimus/uso terapéutico , Quimioterapia de Inducción/métodos , Inducción de Remisión/métodosRESUMEN
Importance: Disparities in outcomes exist between Black and White patients with acute myeloid leukemia (AML), with Black patients experiencing poorer prognosis compared with their White counterparts. Objective: To assess whether varying intensity of induction therapy to treat pediatric AML is associated with reduced disparities in treatment outcome by race. Design, Setting, and Participants: A comparative effectiveness analysis was conducted of 86 Black and 359 White patients with newly diagnosed AML who were enrolled in the AML02 trial from 2002 to 2008 or the AML08 trial from 2008 to 2017. Statistical analysis was conducted from July 2023 through January 2024. Interventions: Patients in AML02 were randomly assigned to receive standard low-dose cytarabine-based induction therapy or augmented high-dose cytarabine-based induction therapy, whereas patients in AML08 received high-dose cytarabine-based therapy. Main Outcomes and Measures: Cytarabine pharmacogenomic 10-single-nucleotide variant (ACS10) scores were evaluated for association with outcome according to race and treatment arm. Results: This analysis included 86 Black patients (mean [SD] age, 8.8 [6.5] years; 54 boys [62.8%]; mean [SD] leukocyte count, 52â¯600 [74â¯000] cells/µL) and 359 White patients (mean [SD] age, 9.1 [6.2] years; 189 boys [52.6%]; mean [SD] leukocyte count, 54â¯500 [91â¯800] cells/µL); 70 individuals with other or unknown racial and ethnic backgrounds were not included. Among all patients without core binding factor AML who received standard induction therapy, Black patients had significantly worse outcomes compared with White patients (5-year event-free survival rate, 25% [95% CI, 9%-67%] compared with 56% [95% CI, 46%-70%]; P = .03). By contrast, among all patients who received augmented induction therapy, there were no differences in outcome according to race (5-year event-free survival rate, Black patients, 50% [95% CI, 38%-67%]; White patients, 48% [95% CI, 42%-55%]; P = .78). Among patients who received standard induction therapy, those with low ACS10 scores had a significantly worse 5-year event-free survival rate compared with those with high scores (42.4% [95% CI, 25.6%-59.3%] and 70.0% [95% CI, 56.6%-83.1%]; P = .004); however, among patients who received augmented induction therapy, there were no differences in 5-year event-free survival rates according to ACS10 score (low score, 60.6% [95% CI, 50.9%-70.2%] and high score, 54.8% [95% CI, 47.1%-62.5%]; P = .43). Conclusions and Relevance: In this comparative effectiveness study of pediatric patients with AML treated in 2 consecutive clinical trials, Black patients had worse outcomes compared with White patients after treatment with standard induction therapy, but this disparity was eliminated by treatment with augmented induction therapy. When accounting for ACS10 scores, no outcome disparities were seen between Black and White patients. Our results suggest that using pharmacogenomics parameters to tailor induction regimens for both Black and White patients may narrow the racial disparity gap in patients with AML.