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Neoplasias Encefálicas , Glioblastoma , Temozolomida , Glioblastoma/tratamiento farmacológico , Glioblastoma/mortalidad , Temozolomida/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Humanos , Biguanidas/uso terapéutico , Animales , Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Metaanálisis como AsuntoRESUMEN
While pancreatic adenocarcinoma requires surgical resection definitive cure, treatment paradigms are shifting toward a neoadjuvant approach to systemic therapy. Rationale is twofold: micro-metastatic disease is likely present in a majority of patients, reinforcing the importance of systemic therapy regardless of resectability; moreover, systemic therapy is well-tolerated and improves surgical outcomes when delivered preoperatively. Second, a neoadjuvant approach allows for selection of biology and patients most likely to benefit from potentially morbid surgery. This review examines the increasing body of evidence in support of empiric neoadjuvant therapy in pancreatic adenocarcinoma.
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Adenocarcinoma , Terapia Neoadyuvante , Pancreatectomía , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirugía , Terapia Neoadyuvante/métodos , Adenocarcinoma/terapia , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Pancreatectomía/métodos , Quimioterapia Adyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Tyrosine kinase inhibitors (TKIs) have revolutionized Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treatment. The combination of blinatumomab and a TKI in the frontline setting has shown the safety and efficacy of the chemotherapy-free treatment approach in patients with Ph + ALL. This retrospective analysis included 19 patients with Ph + ALL and Ph-like ALL treated with the combination of blinatumomab and a TKI. Of the 14 newly diagnosed patients, the overall response, complete remission (CR), and molecular response (CMR) rates after one cycle of blinatumomab were 100% (10/10), 90% (9/10), and 57% (8/14), respectively. Of the five relapsed patients, the CR and CMR rates were 50% (2/4) and 40% (2/5). Blinatumomab in combination with TKIs is safe and effective and hence this combination therapy could be a viable therapeutic option in front-line treatment of patients with Ph + ALL.
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Anticuerpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Inhibidores de Proteínas Quinasas , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Masculino , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Resultado del Tratamiento , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: High-grade endometrial cancers (EAC) are aggressive tumors with a high risk of progression after treatment. As EAC may harbor mutations in the RAS/MAPK pathways, we evaluated the preclinical in vitro and in vivo efficacy of avutometinib, a RAF/MEK clamp, in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718, against multiple primary EAC cell lines and xenografts. METHODS: Whole-exome sequencing (WES) was used to evaluate the genetic landscape of five primary EAC cell lines. The in vitro activity of avutometinib and defactinib as single agents and in combination was evaluated using cell viability, cell cycle, and cytotoxicity assays. Mechanistic studies were performed using Western blot assays while in vivo experiments were completed in UTE10 engrafted mice treated with either vehicle, avutometinib, VS-4718, or their combination through oral gavage. RESULTS: WES results demonstrated multiple EAC cell lines to harbor genetic derangements in the RAS/MAPK pathway including KRAS/PTEN/PIK3CA/BRAF/ARID1A, potentially sensitizing to FAK and RAF/MEK inhibition. Five out of five of the EAC cell lines demonstrated in vitro sensitivity to FAK and/or RAF/MEK inhibition. By Western blot assays, exposure of EAC cell lines to defactinib, avutometinib, and their combination demonstrated decreased phosphorylated FAK (p-FAK) as well as decreased p-MEK and p-ERK. In vivo the combination of avutometinib/VS-4718 demonstrated superior tumor growth inhibition compared to single-agent treatment and controls starting at Day 9 (p < 0.02 and p < 0.04) in UTE10 xenografts. CONCLUSIONS: Avutometinib, defactinib, and to a larger extent their combinations, demonstrated promising in vitro and in vivo activity against EAC cell lines and xenografts. These preclinical data support the potential clinical evaluation of this combination in high-grade EAC patients.
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Neoplasias Endometriales , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Humanos , Animales , Ratones , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Neoplasias Endometriales/genética , Línea Celular Tumoral , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Secuenciación del Exoma , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proliferación Celular/efectos de los fármacos , Clasificación del Tumor , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Oxazepinas , Sulfonamidas , Pirazinas , Benzamidas , ImidazolesRESUMEN
BACKGROUND: Familial adenomatous polyposis is characterized by the presence of multiple colorectal adenomatous polyps and caused by germline mutations in the tumor suppressor gene and adenomatous polyposis coli, located on chromosome 5q21-q22. Familial adenomatous polyposis occurs in approximately 1/10,000 to 1/30,000 live births, and accounts for less than 1% of all colorectal cancers in the USA. It affects both sexes equally and has a worldwide distribution. The incidence of colon cancer in low- and middle-income countries is rising. In addition to the increasing incidence, lack of early detection and impeded access to optimal multidisciplinary treatment may worsen survival outcomes. Developing quality diagnostic services in the proper health context is crucial for early diagnosis and successful therapy of patients with colorectal cancer, and applying a resource-sensitive approach to prioritize essential treatments on the basis of effectiveness and cost-effectiveness is key to overcoming barriers in low- and middle-income countries. We report a case of familial adenomatous polyposis presenting as adenocarcinoma with multiple colorectal adenomatous polyps. The diagnosis of familial adenomatous polyposis was made by the presence of numerous colorectal adenomatous polyps and family history of colonic adenocarcinoma. Due to its rarity, we decided to report it. CASE PRESENTATION: A 22-year-old Ethiopian female patient presented to Addis Ababa University College of Health science, Addis Ababa, Ethiopia with rectal bleeding. Abdominopelvic computed tomography scan was done and showed distal rectal asymmetric anterior wall thickening in keeping with rectal tumor. Colonoscopy was done and she was diagnosed to have familial adenomatous polyposis with severe dysplasia. In the meantime, colonoscopy guided biopsy was taken and the diagnosis of adenocarcinoma with familial adenomatous polyposis was rendered. For this, total proctocolectomy was carried out. On laparotomy there was also incidental finding of left ovarian deposition for which left salpingo-oophorectomy was done, and 4 weeks after surgical resection, the patient was started on oxaliplatin, leucovorin, fluorouracil chemotherapy regimen. CONCLUSION: In the clinical evaluation of a patient with rectal bleeding, familial adenomatous polyposis must be considered as a differential diagnosis in subjects having family history of colonic adenocarcinoma for early diagnostic workup, management, family genetic counseling, and testing.
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Poliposis Adenomatosa del Colon , Humanos , Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/complicaciones , Poliposis Adenomatosa del Colon/terapia , Femenino , Adulto Joven , Adenocarcinoma/diagnóstico , Colonoscopía , Hemorragia Gastrointestinal/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , EtiopíaRESUMEN
Carcinoma of the colon and rectum, also known as colorectal cancer, ranks as the third most frequently diagnosed malignancy globally. Sorafenib exhibits broad-spectrum antitumor activity against Raf, VEGF, and PDGF pathways in hepatocellular, thyroid, and renal cancers, but faces resistance in colorectal malignancies. 6-Shogaol, a prominent natural compound found in Zingiberaceae, exhibits antioxidant, anti-inflammatory, anticancer, and antiemetic properties. We investigated the influence of 6-shogaol on sorafenib's cytotoxic profile against colorectal cancer cell lines (HT-29, HCT-116, CaCo-2, and LS174T) through its effects on cellular accumulation and metabolism. Cytotoxicity was assessed using the sulpharodamine B assay, caspase-3 and c-PARP cleavage, cell cycle distribution analysis, and P-gp efflux activity. 6-Shogoal showed considerable cytotoxicity with decreased IC50 in colorectal cancer cell lines. Combining sorafenib and 6-shogaol increased c-PARP and pro-caspase-3 concentrations in HCT-116 cells compared to sorafenib alone. In combination, pro-caspase-3 concentrations were decreased in CaCo-2 cells compared to alone. Sorafenib combinations with 6-shogaol showed a significant drop in cell cycle distribution from 16.96±1.10â¯% to 9.16±1.85â¯%, respectively. At 100⯵M, sorafenib and 6-shogaol showed potent and significant activity with intra-cellular rhodamine concentration on P-gp efflux activity in CRC cell lines. In conclusion, 6-shogaol substantially improved the cytotoxic profile of sorafenib by affecting its cellular uptake and metabolism. Future research should focus on dosage optimization and formulation and evaluate the efficacy and safety of the combination in animal models with colorectal cancer.
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Catecoles , Neoplasias Colorrectales , Sorafenib , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Sorafenib/farmacología , Catecoles/farmacología , Antineoplásicos/farmacología , Sinergismo Farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Células CACO-2 , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
INTRODUCTION: Predictive markers of LV5FU2 maintenance benefit after first-line induction with FOLFIRINOX in patients with metastatic pancreatic cancer are necessary to select patients who will not be harmed by this strategy. PATIENTS AND METHODS: We focused on patients who received 12 cycles of FOLFIRINOX (arm A, Nâ =â 88) or 8 cycles of FOLFIRINOX followed by LV5FU2 maintenance in controlled patients (arm B, Nâ =â 91) from the PRODIGE-35 trial. Prognostic factors and predictors of efficiency were identified by using Cox regression. Median progression-free survival (PFS), overall survival (OS), and time to deterioration of quality of life (TTD-QoL) were evaluated. RESULTS: Poor independent prognostic factors were primary tumor in place, age <65 years and the presence of liver metastases for PFS, a baseline neutrophil/lymphocyte ratio (NLR) ≥5 and CA19.9 ≥500 UI/L for OS, independent of the treatment arm. Patients with one metastatic site had a longer PFS in arm A, whereas patients with ≥2 metastatic sites had a longer PFS in arm B. We also identified predictors of OS and TTD-QoL in arm B but these differences were not statistically significant. CONCLUSION: Except for patients with one metastatic site who benefited more from 12 cycles of FOLFIRINOX, a maintenance strategy with LV5FU2 should be widely offered to mPC patients whose survival and QoL are preserved after 4 months of FOLFIRINOX. (ClinicalTrials.gov: NCT02352337).
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Irinotecán , Leucovorina , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Masculino , Femenino , Persona de Mediana Edad , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Pronóstico , Calidad de Vida , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Adulto , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: This study aims to evaluate the short-term efficacy for locally advanced gastric cancer (LAGC) who accepted laparoscopic gastrectomy (LG) after neoadjuvant SOX versus SOX plus immune checkpoint inhibitors (ICIs). METHODS: LAGC patients who accepted LG after neoadjuvant SOX (SOX-LG, n = 169) and SOX plus ICIs (SOX + ICIs-LG, n = 140) in three medical centers between Jan 2020 and Mar 2024 were analyzed. We compared the tumor regression, treatment-related adverse events (TRAEs), perioperative safety between two groups, and explored the risk factors of postoperative complications (POCs) for LG after neoadjuvant therapy. RESULTS: The baseline characteristics were comparable between two groups (P > 0.05). SOX + ICIs-LG group acquired a higher proportion of objective response (63.6% vs. 46.7%, P = 0.003), major pathological response (43.6% vs. 31.4%, P = 0.001), and pathological complete response (17.9% vs. 9.5%, P = 0.030). There were no significant differences in the TRAEs rates, operation time, R0 resection, retrieved lymph nodes, postoperative first flatus, and hospitalized days, overall and severe POCs between two groups (P > 0.05). Patients in the SOX-ICIs-LG group had lower estimated blood loss (EBL) compared with SOX-LG (P = 0.001). Multivariate analysis showed that more EBL (P = 0.003) and prognostic nutritional index (PNI) < 40 (P = 0.005) were independent risk factors of POCs for LG after neoadjuvant therapy. CONCLUSION: Neoadjuvant SOX plus ICIs brings better tumor regression and similar TRAEs compared with SOX alone for LAGC. SOX + ICIs-LG is safe and feasible to conduct with less EBL. Surgeons should focus on the perioperative management to control POCs for patients with PNI < 40 and more EBL.
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Gastrectomía , Inhibidores de Puntos de Control Inmunológico , Laparoscopía , Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Masculino , Femenino , Gastrectomía/métodos , Gastrectomía/efectos adversos , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , China/epidemiología , Laparoscopía/métodos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , AdultoRESUMEN
BACKGROUND: Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MER), VEGFR-2, KIT, and MET. SAFFRON-104 (NCT03941873) was a multicohort phase Ib/II study investigating sitravatinib with/without tislelizumab, an anti-programmed cell death protein 1 (PD-1) antibody, in patients with advanced hepatocellular carcinoma (HCC) or gastric cancer/gastroesophageal junction cancer (GC/GEJC). METHODS: Eligible patients had histologically/cytologically confirmed advanced HCC or GC/GEJC. Phase I determined the recommended phase II dose (RP2D) of sitravatinib with/without tislelizumab. Phase II evaluated sitravatinib monotherapy in patients with pretreated HCC, and sitravatinib plus tislelizumab in anti-PD-(L)1-naïve or -treated HCC and anti-PD-(L)1-naïve GC/GEJC. Primary endpoints were safety/tolerability (phase I) and objective response rate (ORR) (phase II). RESULTS: At data cutoff (March 31, 2023), 111 patients were enrolled; 102 were efficacy-evaluable (median study follow-up 9.1 months [range: 0.7-36.9]). The RP2D of sitravatinib was determined as 120 mg orally once daily. In patients receiving sitravatinib monotherapy and sitravatinib in combination with tislelizumab, grade ≥ 3 treatment-related adverse events occurred in 14 (51.9%) and 42 (50.0%) patients, respectively. The ORR was 25% (95% confidence interval [CI]: 8.7-49.1) in patients with pretreated HCC receiving sitravatinib monotherapy. In patients receiving sitravatinib with tislelizumab, the ORR was 11.5% (95% CI 2.4-30.2) with anti-PD-(L)1-naïve HCC, 9.5% (95% CI 1.2-30.4) with anti-PD-(L)1-treated HCC, and 16.1% (95% CI 5.5-33.7) in patients with anti-PD-(L)1-naïve GC/GEJC. CONCLUSIONS: Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC.
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Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Unión Esofagogástrica , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacología , Anciano , Persona de Mediana Edad , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Unión Esofagogástrica/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking. METHODS: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing. RESULTS: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival. CONCLUSION: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Humanos , Masculino , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/genética , Adulto , PronósticoAsunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiple , Talidomida , Humanos , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Talidomida/análogos & derivados , Talidomida/administración & dosificación , Talidomida/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacosRESUMEN
BACKGROUND: Treatment of brain metastases (BMs) in non-small cell lung cancer (NSCLC) patients, especially those with non-sensitive genetic mutations, is hindered by limited drug delivery through the blood-brain barrier (BBB). This retrospective study explores the efficacy of systemic treatments during brain metastasis to radiotherapy evaluation window in improving patient survival. METHODS: In this retrospective cohort study, we evaluated 209 NSCLC patients with non-sensitive mutations and BMs, treated between 2016 and 2023 at two tertiary medical centers (Chongqing University Cancer Hospital and Guangxi Medical University Cancer Hospital). The patients were divided into three groups, namely chemotherapy alone (C; n = 95), chemotherapy plus immune checkpoint inhibitors (ICIs) (C + I; n = 62), and chemotherapy with ICIs and antiangiogenic therapy (A) (C + I + A; n = 52). Statistical analyses were performed using R software, version 4.3.3. Categorical variables were compared using Fisher's exact test, and survival curves were estimated with the Kaplan-Meier method and compared via the log-rank test. Univariate and multivariate Cox regression models were used to assess factors associated with overall survival (OS). Bayesian model averaging (BMA) was employed to address model uncertainty and improve result robustness. Subgroup analyses evaluated treatment-related mortality risk. RESULTS: From an initial cohort of 658 NSCLC patients with BMs, 209 were analyzed with a median age of 59; the majority were male (80.9%) and diagnosed with adenocarcinoma (78.9%). Univariate analysis identified significant variables influencing outcomes, including BMs radiotherapy EQD2, BMs count, local thoracic treatment, BMs radiotherapy field, intracranial response, and systemic treatment post-BMs diagnosis. The C + I + A regimen significantly improved median OS to 23.6 months compared to 11.4 months with C and 16.2 months with C + I, with a hazard ratio (HR) of 0.60 (95% CI: 0.43-0.82; P < 0.0001). The two-year OS rate was highest in the C + I + A group at 38.5%, versus 10.5% in C and 20.4% in C + I (P < 0.001). Cox regression and BMA analyses confirmed the stability of BMA in providing HR estimates, yielding area under the curve (AUC) values of 0.785 for BMA and 0.793 for the Cox model, with no significant difference in predictive performance. Subgroup analysis revealed a 71% mortality risk reduction with C + I + A (HR: 0.29; 95% CI: 0.18-0.47; P < 0.0001), showing consistent benefits regardless of patient sex, BMs count, extracranial metastases presence, and local thoracic treatments. Treatment sequence analysis indicated a median OS of 33.4 months for patients starting with A, though not statistically significant (HR: 0.59; P = 0.36). The overall incidence of radiation-induced brain injury was low at 3.3%, with rates in the C, C + I, and C + I + A groups being 3.2%, 4.8%, and 1.9%, respectively (P = 0.683). CONCLUSION: Our study demonstrates the significant benefit of the C + I + A combination therapy in improving OS and reducing mortality risk in NSCLC patients with non-sensitive gene-mutated BMs. The sequential administration of A followed by ICIs shows a promising synergistic effect with cranial radiotherapy, highlighting the potential for optimized treatment sequencing. These findings emphasize the efficacy of tailored combination therapies in complex oncological care and suggest that our approach could lead to meaningful improvements in clinical outcomes for this challenging patient population.
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Inhibidores de la Angiogénesis , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios Retrospectivos , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/tratamiento farmacológico , Masculino , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Inhibidores de la Angiogénesis/uso terapéutico , Anciano , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , AdultoRESUMEN
OBJECTIVES: Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group. METHODS: A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS). RESULTS: A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified. CONCLUSIONS: The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Pancreáticas , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/mortalidad , Procedimientos Quirúrgicos de Citorreducción/métodos , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Masculino , Femenino , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Quimioterapia Intraperitoneal Hipertérmica/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Tasa de Supervivencia , Terapia Combinada , Pronóstico , Anciano , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , AdultoRESUMEN
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.
Asunto(s)
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 RemisiónAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Linfocítica Crónica de Células B , Sulfonamidas , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inducción de Remisión , Terapia Molecular Dirigida/métodosAsunto(s)
Acrilamidas , Compuestos de Anilina , Neoplasias Pulmonares , Supervivencia sin Progresión , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Acrilamidas/uso terapéutico , Compuestos de Anilina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Indoles , PirimidinasRESUMEN
Therapy-related acute myeloid leukemia (t-AML) often exhibits adverse (genetic) features. There is ongoing discussion on the impact of t-AML on long-term outcome in AML. Therefore, we retrospectively analyzed clinical and biological characteristics of 1133 AML patients (225 t-AML patients and 908 de novo AML patients) with a median follow-up of 81.8 months. T-AML patients showed more adverse genetic alterations, higher age and more comorbidities as compared to de novo AML. Median OS in intensively treated t-AML patients was 13.7 months as compared to 39.4 months in de novo AML (p < 0.001). With non-intensive therapy, OS did not differ significantly (p = 0.394). With intensive therapy, significant differences in favor of de novo AML were observed in the ELN intermediate I/II (p = 0.009) and adverse (p = 0.016) risk groups but not within favorable risk groups (APL p = 0.927, ELN favorable p = 0.714). However, t-AML was no independent risk factor for OS (p = 0.103), RR (p = 0.982) and NRM (p = 0.320) in the multivariate analysis. A limitation of our study is an ELN 2010 risk stratification due to a lack of more comprehensive molecular data according to ELN 2022. We conclude that therapeutic algorithms in t-AML, in particular with regard to allo-HSCT, should be guided by ELN genetic risk rather than classification as t-AML alone. Our data support the WHO and ICC 2022 classifications, which include t-AML as diagnostic qualifier rather than a separate subcategory.
Asunto(s)
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Estudios Retrospectivos , Adulto Joven , Anciano de 80 o más Años , Adolescente , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Resultado del Tratamiento , Pronóstico , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoAsunto(s)
Sinergismo Farmacológico , Leucemia Mieloide Aguda , Mutación , Inhibidores de Proteínas Quinasas , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Quinasa Activadora de Quinasas Ciclina-Dependientes , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Given the early use of triplet and quadruplet regimens, most patients with multiple myeloma (MM) will be exposed and/or refractory to PIs, IMiDs, and anti-CD38 mAbs after first- or second-line treatment. Effective treatment for this group of triple class exposed/refractory (TCE/R) patients is crucial. Here we present a post-hoc subgroup analysis of TCE/R patients treated on the ALGONQUIN study of belantamab mafodotin plus pomalidomide-dexamethasone (belamaf-Pd) for relapsed MM. Of the 99 patients treated on the ALGONQUIN study, 69 were TCE and 56 were TCR and were included in this analysis. Patients had a median of three prior lines of therapy. The ORR was 86.4% in TCE patients and 84.9% in TCR patients, with ≥ very good partial response rates of 64% and 68% respectively. The median progression free survival was 18.3 months in TCE patients and 19.6 months in TCR patients, with overall survival not yet reached and 34.4 months, respectively for TCE and TCR patients. No new safety signals were identified. The most common Grade ≥ 3 AEs were keratopathy (48%), decreased visual acuity (42%), neutropenia (36%), thrombocytopenia (27%), and infection (25%). In this subgroup analysis of the ALGONQUIN study, patients with TCE/TCR disease treated with belamaf-Pd achieved high clinical response rates with durable remissions, comparable to other novel therapeutics in this space.