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Duodenal adenocarcinoma is a rare and aggressive gastrointestinal malignancy that frequently presents with symptoms like gastric outlet obstruction and biliary obstruction, leading to delayed diagnosis and challenging prognosis. This case report explores the clinical presentation, diagnostic hurdles, and therapeutic management of late-stage duodenal adenocarcinoma in a 53-year-old woman with no significant prior medical history. The patient presented with severe epigastric pain radiating to the right upper quadrant, nausea, and decreased appetite. Elevated liver enzymes and imaging revealed multiple liver masses and a primary duodenal mass. Biopsies confirmed moderately differentiated adenocarcinoma. Tumor markers were evaluated during the staging phase, showing markedly elevated levels. The patient underwent systemic chemotherapy with FOLFOX but faced complications, including pulmonary emboli and neurological symptoms. Management required a multidisciplinary approach, integrating palliative and supportive care to address symptoms and improve quality of life. The case highlights the necessity of considering duodenal adenocarcinoma when diagnosing persistent gastrointestinal symptoms. It highlights the need for a holistic treatment approach, including tailored chemotherapy regimens and vigilant monitoring of complications. Molecular profiling was crucial in guiding treatment decisions, although MSI, HER2, and PD-1 were negative, and the tumor showed no mismatch repair protein deficiency. This article emphasizes the importance of early integration of palliative care and the value of comprehensive pathological analysis in managing advanced duodenal adenocarcinoma, providing insights into diagnostic and therapeutic strategies for this complex case.
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BACKGROUND: 5-Fluorouracil (5-FU) is a major component of gastrointestinal cancer treatments. In multidrug regimens such as FOLFOX, FOLFIRI, and FOLFIRINOX, 5-FU is commonly administered as a bolus followed by an infusion. However, the pharmacologic rationale for incorporating the 5-FU bolus in these regimens is unclear, and there are other effective regimens for gastrointestinal cancers that do not include the bolus. The purpose of this study was to determine whether omission of the 5-FU bolus was associated with a difference in survival and toxicity. METHODS: A real-world database from Flatiron Health was queried for patients with advanced colorectal, gastroesophageal, and pancreatic cancers who received first-line FOLFOX, FOLFIRI, and FOLFIRINOX regimens. Cox proportional hazards and Kaplan-Meier analyses were performed to compare survival outcomes between patients who received the 5-FU bolus and those who did not. Inverse probability of treatment weighted (IPTW) analysis was performed to adjust for treatment selection bias. RESULTS: This study included 11,765 patients with advanced colorectal (n=8,670), gastroesophageal (n=1,481), and pancreatic (n=1,614) cancers. Among all first-line 5-FU multidrug regimens, 10,148 (86.3%) patients received a 5-FU bolus and 1,617 (13.7%) did not. After IPTW analysis, we found that omitting the bolus was not associated with a decrease in overall survival (hazard ratio, 0.99; 95% CI, 0.91-1.07; P=.74). However, omitting the bolus was associated with reductions in neutropenia (10.7% vs 22.7%; P<.01), thrombocytopenia (11.2% vs 16.1%; P<.01), and use of granulocyte colony-stimulating factors after treatment (19.6% vs 29.1%; P<.01). CONCLUSIONS: After adjusting for baseline clinical factors, we found that omission of the 5-FU bolus from FOLFOX, FOLFIRI, and FOLFIRINOX regimens was not associated with decreased survival, but resulted in decreased toxicity and possible health care savings.
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BACKGROUND: Synthetic lethality (SL) emerges as a novel concept being explored to combat cancer progression and resistance to conventional therapy. Despite the efficacy of chemotherapy in select cases of colorectal cancer (CRC), a substantial proportion of patients encounter challenges, leading to an adverse prognosis of CRC patients. CRC-related SL genes offer a potential avenue for identifying therapeutic targets. METHODS: CRC-related SL genes were obtained from the SynLethDB database. The bulk RNA sequencing data, mutation data, and clinical information for treated and untreated CRC patients were enrolled from the UCSC and GEO databases. The Tumor Immunology Single Cell Center database served as the repository for collecting and analyzing single-cell RNA sequencing data. The synergistic killing effect of SL genes and chemotherapeutic drugs on resistant cells was experimentally verified. RESULTS: In the present study, pivotal SL genes associated with chemoresistance identified by using WGCNA and CRC patients categorized into two groups based on these genes. Variations between the groups were most pronounced in pathways associated with extracellular matrix remodeling. Further by integrating mutation data, five potential SL genes were discerned, which were highly expressed in the presence of TP53 or KRAS mutations, leading to a severely poor prognosis. Subsequent time series analysis revealed that the expression of GTF2H5 was gradually elevated at different stages of the transition from sensitive to resistant in CRC cells. Finally, it was preliminarily verified by experiments that GTF2H5 may play a key role in driving the drug-resistant transition within CRC cells. CONCLUSIONS: The identification of SL genes that collaboratively interact with chemotherapeutic agents could provide new insights into solving the issue of chemotherapy resistance in CRC patients. And GTF2H5 wields a fundamental influence in inducing chemoresistance in CRC, which provided a potential therapeutic target for CRC.
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BACKGROUND: Colorectal cancer (CRC) is a significant malignancy with widespread implications. Despite progress in surgical interventions for rectal cancer, improvements in overall prognosis remain disproportionate. Standard preoperative chemoradiation, while established as the standard treatment for the majority of rectal cancers, exhibits limited effectiveness in enhancing disease-free survival (DFS) and mitigating distant metastases, particularly in cases of locally advanced rectal cancer (LARC). METHODS: This randomised clinical trial assessed 286 patients with LARC in two paralleled groups. Group A underwent six courses of neoadjuvant MFOLFOX chemotherapy, chemoradiation, surgery, and six adjuvant chemotherapy cycles. Group B received concurrent chemoradiation, surgery, and twelve adjuvant chemotherapy cycles. Patient evaluations were achieved at multiple stages of treatment and follow-up. RESULTS: Group A had significantly lower local recurrence (11.64%) than Group B (21.74%, P = 0.025). The distant metastasis rate in Group A (8.90%) was lower than in Group B (20.29%) but was not significant (p = 0.143). More patients in Group A experienced downstaging (80.82% vs. 60.87%, p < 0.001). Specifically, 72.60% demonstrated downstaging of tumour invasion and 54.79% downstaging of lymph node involvement, compared to 57.25% and 41.30% in Group B (p = 0.009 and p = 0.025, respectively) as well as higher pCR rate (26.03% vs. 15.25%, p = 0.030) and three-year DFS rate (82.19% vs. 71.01%, p = 0.035) in group A compare to group B. CONCLUSION: This innovative strategy for LARC showed promising results with lower local recurrence and higher rates of downstaging and pCR. Treatment side effects were similar in both groups but less frequent in Group A. Anaemia was the most common haematological side effect (A: 58%, B: 68%), and peripheral sensory neuropathy was the most common non-haematological complication (A: 63%, B: 64%). These findings suggest this regimen could be a valuable therapeutic approach for LARC. TRIAL REGISTRATION: This trial was registered on 2023-12-08 within the IRCT.IR database under the number IRCT20210308050628N1.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Leucovorina , Terapia Neoadyuvante , Compuestos Organoplatinos , Neoplasias del Recto , Humanos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Neoplasias del Recto/mortalidad , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Quimioterapia Adyuvante/métodos , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Adulto , Anciano , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resultado del Tratamiento , Supervivencia sin EnfermedadRESUMEN
The malignant transformation of mature cystic teratomas during pregnancy is a rare occurrence in medical literature. In this case report, we present a remarkable instance of mucinous intestinal adenocarcinoma arising from a mature ovarian cystic teratoma diagnosed during pregnancy. This is among the few reports detailing the effective use of the FOLFOX 6 chemotherapy regimen for treating this type of intestinal cancer. Furthermore, we emphasize the immunohistochemical results that confirm the colorectal histological origin.
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BACKGROUND: Although chemotherapy is effective for treating advanced gastric carcinoma (aGC), it may lead to an adverse prognosis. Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients. AIM: To determine the efficacy and safety of cetuximab (CET) combined with the FOLFOX4 regimen (infusional fluorouracil, folinic acid, and oxaliplatin) as first-line therapy for patients with aGC, who received evidence-based care (EBC). METHODS: A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled. Of these, 60 in the research group (RG) received CET + FOLFOX4 as first-line therapy, whereas 57 in the control group (CG) received FOLFOX4. The efficacy [clinical response rate (RR) and disease control rate (DCR)], safety (liver and kidney dysfunction, leukopenia, thrombocytopenia, rash, and diarrhea), serum tumor marker expression [STMs; carbohydrate antigen (CA) 19-9, CA72-4, and carcinoembryonic antigen (CEA)], inflammatory indicators [interleukin (IL)-2 and IL-10], and quality of life (QOL) of the two groups were compared. RESULTS: A markedly higher RR and DCR were observed in the RG compared with the CG, with an equivalent safety profile between the two groups. RG exhibited notably reduced CA19-9, CA72-4, CEA, and IL-2 levels following treatment, which were lower than the pre-treatment levels and those in the CG. Post-treatment IL-10 was statistically increased in RG, higher than the pre-treatment level and the CG. Moreover, a significantly improved QOL was evident in the RG. CONCLUSION: The CET + FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC. It facilitates the suppression of STMs, ameliorates the serum inflammatory microenvironment, and enhances QOL, without increased adverse drug effects.
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BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated. PATIENTS AND METHODS: PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses. RESULTS: Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses. CONCLUSIONS: Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.
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FOLFOX is a combination of chemotherapeutic agents (5-fluorouracil, leucovorin, and oxaliplatin) and is used to treat advanced colorectal cancer (CRC) but induces various side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most critical side effects that compromise the quality of life of patients with CRC undergoing FOLFOX chemotherapy. This study aimed to evaluate circulating miRNA, cortisol and catecholamine as potential biomarkers that can predict FOLFOX-CIPN symptoms. High-throughput microRNA (miRNA) sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤3 cycles and those who underwent ≥6 cycles of FOLFOX chemotherapy. The identified miRNAs were validated in 27 patients with CRC who underwent FOLFOX chemotherapy using quantitative reverse transcription polymerase chain reaction. Target genes were predicted using bioinformatics and functional analyses. Cortisol and catecholamine concentrations in peripheral plasma were measured using an enzyme-linked immunosorbent assay. miR-3184-5p was differentially expressed when miRNA expression was compared between the groups that underwent ≤3 and ≥6 cycles of FOLFOX chemotherapy. Cortisol levels were significantly higher in the group that underwent ≥6 cycles of FOLFOX chemotherapy than in the group that underwent ≤3 cycles. This study suggests that miR-3184-5p may be a potential marker for predicting CIPN.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Fluorouracilo , Leucovorina , MicroARNs , Compuestos Organoplatinos , Enfermedades del Sistema Nervioso Periférico , Humanos , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Enfermedades del Sistema Nervioso Periférico/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/sangre , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , MicroARNs/sangre , MicroARNs/genética , Anciano , Hidrocortisona/sangre , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Adulto , Catecolaminas/sangreRESUMEN
Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.
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Aminoácidos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Fluorouracilo , Oxaloacetatos , Humanos , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Masculino , Femenino , Persona de Mediana Edad , Aminoácidos/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Capecitabina/uso terapéutico , Malondialdehído/sangre , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Compuestos Organoplatinos/uso terapéutico , Proyectos Piloto , Oxidación-Reducción , Adulto , Peroxidación de Lípido/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
A 52-year-old male patient was diagnosed with transverse colon cancer and synchronous stage IVA para-aortic lymph node (PALN) metastases (cT3N1bM1a of the lymph node). Six courses of mFOLFOX6 plus bevacizumab were administered as neoadjuvant chemotherapy. Computed tomography showed shrinkage of the primary tumor and PALN metastases. Extended right hemicolectomy, D3 lymph node dissection, and PALN dissection were performed. A pathologic examination indicated that the tumor had completely changed and comprised necrotic tissue with no viable cells. Therefore, it was considered that mFOLFOX6 plus bevacizumab resulted in a pathologic complete response. Postoperatively, six courses of mFOLFOX6 were administered. Six years postoperatively, the patient did not exhibit any signs of recurrence. There have been few reports of pathologic complete response after neoadjuvant therapy and resection for colon cancer with synchronous PALN metastases. This report describes a unique case involving a pathologic complete response with long-term survival after mFOLFOX6 plus bevacizumab and radical resection, including PALN dissection. Preoperative mFOLFOX6 plus bevacizumab followed by radical resection and adjuvant mFOLFOX6 therapy was safe and resulted in a good outcome. This regimen should be considered for advanced colon cancer with PALN metastases.
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Background: Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy characterized by high incidence rates and a poor prognosis. Common treatment modalities include surgery, ablation, and transarterial chemoembolization (TACE). Hepatic arterial infusion chemotherapy (HAIC) has long been used in the treatment of unresectable liver cancer. In recent years, the combination of anti-angiogenesis therapy and immune checkpoint inhibitors has shown significant advances in the treatment of middle- and advanced-stage liver cancer. This report presents a case of HCC in which sustained benefits are achieved through a combination of HAIC of infusional oxaliplatin, leucovorin, and fluorouracil (FOLFOX), targeted therapy, and immunotherapy. Main body: A 64-year-old male patient was diagnosed with a parenchymal mass in the liver by a three-dimensional color ultrasound one month before admission, prompting consideration of liver cancer. Subsequently, computed tomography (CT) imaging performed at our hospital identified mass shadows in the right lobe of the liver and diffuse nodules throughout the liver, suggesting malignant lesions. Upon admission, the patient presented poor general health and baseline indicators. Following symptomatic treatment, the patient underwent a therapeutic regimen that combined transarterial infusion port FOLFOX-HAIC with Lenvatinib and Sintilimab. This combined treatment resulted in significant liver tumor necrosis and effectively managed the patient's condition. Conclusion: The combined approach of using FOLFO-HAIC transarterial infusion alongside anti-angiogenesis therapy and immune checkpoint inhibitors has shown promising results that provide substantial benefits. This combined regimen has demonstrated the potential to improve treatment compliance among certain patients. Given these encouraging outcomes, further investigation into this combination therapy regimen is warranted to understand better its efficacy and potential broader applications in clinical settings.
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Background: The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) is effective in patients with unresectable ICC. In this study, we determined the preliminary clinical efficacy and safety of lenvatinib plus durvalumab combined with FOLFOX-HAIC in patients with untreated, unresectable ICC. Materials and methods: Between July 2021 and July 2023, patients with unresectable ICC who initially received lenvatinib plus durvalumab combined with FOLFOX-HAIC at the Sun Yat-Sen University Cancer Center (SYSUCC) were reviewed for eligibility. Efficacy was evaluated by tumor response rate and survival, and safety was assessed by the frequency of key adverse events (AEs). Results: A total of 28 eligible patients were enrolled. The objective response rates (ORRs) based on mRECIST and RECIST 1.1 criteria were 65.2% and 39.1%, respectively. The median OS was 17.9 months (95% CI, 5.7-30.1) and the median PFS was 11.9 months (95% CI, 6.7-17.1). Most patients (92.9%) experienced adverse events (AEs), whereas 46.5% (13/28) experienced grade 3 or 4 AEs. Conclusion: Lenvatinib plus durvalumab combined with FOLFOX-HAIC showed promising antitumor activity and manageable AEs in patients with treatment-naive unresectable ICC. This regimen may be suitable as a novel first-line treatment option for this patient population.
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Colangiocarcinoma , Compuestos de Fenilurea , Quinolinas , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Persona de Mediana Edad , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Anciano , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/mortalidad , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Infusiones Intraarteriales , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Adulto , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Resultado del Tratamiento , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/efectos adversos , Arteria Hepática , Estudios RetrospectivosRESUMEN
Objectives: This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. Methods: This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. Results: The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. Conclusions: BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Fluorouracilo , Inmunoterapia , Infusiones Intraarteriales , Leucovorina , Neoplasias Hepáticas , Humanos , Persona de Mediana Edad , Masculino , Femenino , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Anciano , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Inmunoterapia/métodos , Resultado del Tratamiento , Terapia Molecular Dirigida , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Arteria HepáticaRESUMEN
INTRODUCTION: The incidence of primary liver cancer (PLC) has experienced a significant global increase, primarily attributed to the rise in hepatocellular carcinoma (HCC). Unfortunately, HCC is often diagnosed in advanced stages, leaving patients with limited treatment options. Therefore, transformation therapy is a crucial approach for long-term survival and radical resection in patients with advanced HCC. Conversion therapy has demonstrated promise in the treatment of advanced HCC. When integrated with the FOLFOX regimen, hepatic artery infusion chemotherapy (HAIC) can significantly improve tumor response efficiency, leading to high conversion and resection rates. AREAS COVERED: We reviewed landmark trials of HAIC in combination with different drugs or means for the treatment of HCC to determine the clinical value of HAIC-centric translational therapies in HCC treatment. Furthermore, we specifically emphasize the advantages associated with employing FOLFOX-HAIC in the treatment of advanced HCC. EXPERT OPINION: The combination of HAIC with the FOLFOX regimen can help prevent the low intratumoral accumulation and high adverse reaction rate caused by the FOLFOX alone, holding significant potential in the comprehensive treatment of future HCC patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Fluorouracilo , Arteria Hepática , Infusiones Intraarteriales , Leucovorina , Neoplasias Hepáticas , Compuestos Organoplatinos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Fluorouracilo/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Leucovorina/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/farmacología , Tasa de Supervivencia , Estadificación de NeoplasiasRESUMEN
BACKGROUND: No widely used prognostic tool exists to demonstrate the benefit of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) in patients with advanced hepatocellular carcinoma (HCC). We aimed to establish a prognostic score and demonstrate the real-world efficacy of FOLFOX4 chemotherapy in Thai patients. METHODS: Between August 2017 and December 2021, we identified 58 FOLFOX4-treated patients with HCC. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were assessed. The prognostic score was constructed by stepwise Cox proportional hazards regression analysis to select variables for the best model with the lowest Akaike information criterion from all potential variables. RESULTS: Forty-four patients (76%) received FOLFOX4 as first-line therapy. The ORR in the entire cohort was 8.6%, and the disease control rate was 29.3%. The PFS and OS were 3.7 and 4.8 months, respectively. Four clinically relevant variables were included in the new prognostic score to predict 6-month OS: L, the presence of lung metastasis; A, alcoholic cirrhosis; B, elevated total bilirubin level; and S, sorafenib-naïve status. Using the LABS score, patients were classified into low-, intermediate-, and high-risk groups, demonstrating OS values of 9.3, 4.2, and 2.1 months, respectively (p < 0.0001). The C-index and area under the receiver-operating characteristic curve of the score were 0.71 and 0.73, respectively. CONCLUSIONS: The proposed LABS score could discriminate patients who would derive benefit from FOLFOX4 chemotherapy. FOLFOX4 chemotherapy is an option for patients who cannot receive immunotherapy and targeted therapy, particularly those with a low-risk score. However, further validation of this model via larger cohorts is warranted.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias Hepáticas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Fluorouracilo , Leucovorina , Resultado del TratamientoRESUMEN
BACKGROUND: Chemoresistance is a critical factor contributing to poor prognosis in clinical patients with cancer undergoing postoperative adjuvant chemotherapy. The role of gut microbiota in mediating resistance to tumour chemotherapy remains to be investigated. METHODS: Patients with CRC were categorised into clinical benefit responders (CBR) and no clinical benefit responders (NCB) based on chemotherapy efficacy. Differential bacterial analysis using 16S rRNA sequencing revealed Desulfovibrio as a distinct microbe between the two groups. Employing a syngeneic transplantation model, we assessed the effect of Desulfovibrio on chemotherapy by measuring tumour burden, weight, and Ki-67 expression. We further explored the mechanisms underlying the compromised chemotherapeutic efficacy of Desulfovibrio using metabolomics, western blotting, colony formation, and cell apoptosis assays. FINDINGS: In comparison, Desulfovibrio was more abundant in the NCB group. In vivo experiments revealed that Desulfovibrio colonisation in the gut weakened the efficacy of FOLFOX. Treatment with Desulfovibrio desulfuricans elevates serum S-adenosylmethionine (SAM) levels. Interestingly, SAM reduced the sensitivity of CRC cells to FOLFOX, thereby promoting the growth of CRC tumours. These experiments suggest that SAM promotes the growth and metastasis of CRC by driving the expression of methyltransferase-like 3 (METTL3). INTERPRETATION: A high abundance of Desulfovibrio in the intestines indicates poor therapeutic outcomes for postoperative neoadjuvant FOLFOX chemotherapy in CRC. Desulfovibrio drives the manifestation of METTL3 in CRC, promoting resistance to FOLFOX chemotherapy by increasing the concentration of SAM. FUNDING: This study is supported by Wuxi City Social Development Science and Technology Demonstration Project (N20201005).
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Neoplasias Colorrectales , Desulfovibrio desulfuricans , Humanos , Apoptosis , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Desulfovibrio desulfuricans/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Metiltransferasas , ARN Ribosómico 16S/genética , Leucovorina , Compuestos Organoplatinos , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
BACKGROUND/AIM: Definitive chemoradiotherapy with cisplatin (CDDP) plus 5-fluorouracil is the standard treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC); however, CDDP is unsuitable for patients with cardiac and/or renal dysfunction. Based on the results of the PRODIGE5/ACCORD17 trial, 5-fluorouracil and leucovorin with oxaliplatin plus radiotherapy (FOLFOX-RT) has been recognized as a treatment option. However, the efficacy and safety of FOLFOX-RT is still unclear in Japan. PATIENTS AND METHODS: Medical records were reviewed for patients with LA-ESCC who received FOLFOX-RT between April 2019 and July 2021 at our institution. We evaluated complete response rate, progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Fifteen patients were analyzed and median age was 72.5 years (range=51-83 years). All patients completed three courses of FOLFOX and the planned radiotherapy. The complete response rate was 40.0%. With a median follow-up of 10.6 months, the 6-month PFS rate was 63.0% (95%CI=32.3-82.8%), and the 6-month OS rate was 85.7% (95%CI=53.9-96.2%). Common adverse events were esophagitis (80.0%), leukopenia (53.3%), fatigue (53.3%), and neutropenia (46.7%). Only one patient had grade 4 esophageal perforation. CONCLUSION: FOLFOX-RT for LA-ESCC was well tolerated and could be a treatment option for CDDP-intolerant patients.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Anciano , Cisplatino , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Estudios Retrospectivos , Fluorouracilo/efectos adversos , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
FOLFOX regimen, composed of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (OXP), has been used as clinical standard therapeutic regimen in treatments of colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC). To further improve its therapeutic outcomes, FOLFOX was combined with anti-PD-1 antibody to form an advanced chemo-immune combination strategy, which has been proven more efficient in controlling cancer progression and prolonging patients' survival in various clinical trials. However, bad tumor accumulation, relative high toxicity, numerous treatment cycles with high fees and low compliance as well as drug resistance seriously limit the prognosis of FOLFOX regimen. The "all-in-one" formulations, which could precisely delivery multidrug regimen into tumor sites and cells, showed a promising application prospect for targeted drug delivery as well as reducing side effects. However, the design and preparation of the "all-in-one" formulation with high drug encapsulation efficiencies for all drugs was still challenging. Herein, a lipid core-shell nanoparticle codelivery platform was designed for simultaneous encapsulation of variant FOLFOX composed of miriplatin (MiPt), 5-Fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), calcium folinate (CF) and PD-L1 siRNA (siPD-L1) with high efficiencies, and their synergistic anti-tumor mechanisms were studied, respectively. MiPt, a precursor of OXP, was validated capable of inducing efficient immunogenic cell death (ICD) in this work. Additionally, ICD-mediated release of damage associated molecular patterns functionalized synergistically with PD-L1 silence by siPD-L1 to overcome chemoresistance, reverse suppressive tumor microenvironment and recruit more CD8+ T cells. FdUMP, as the intracellular active form of 5-FU, could induce large amounts of reactive oxygen species to enhance the ICD. CF worked as the sensitizer of FdUMP. The enhanced long-term anti-tumor effect of the prepared "all-in-one" formulation compared to free drug regimen and other controls, was verified in heterotopic CRC mice models and ESCC mice models, providing new thoughts for researchers and showing a promising prospect of translation into clinical applications.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Nanopartículas , Humanos , Animales , Ratones , Leucovorina/uso terapéutico , Antígeno B7-H1 , Neoplasias Colorrectales/patología , Linfocitos T CD8-positivos/patología , Fluorodesoxiuridilato/uso terapéutico , Fluorouracilo/uso terapéutico , Oxaliplatino , Lípidos/uso terapéutico , Línea Celular Tumoral , Inmunoterapia , Compuestos OrganoplatinosRESUMEN
Liver transplantation (LT) is the primary treatment for patients with early-stage hepatocellular carcinoma (HCC). However, the 5-year survival rate after LT remains low for patients with advanced HCC. Recently, combining programmed cell death protein-1 (PD-1) inhibitors with hepatic arterial infusion chemotherapy (HAIC) has achieved promising outcomes in advanced HCC treatment. However, there is a lack of sufficient clinical data demonstrating its effectiveness as a pre-LT down-staging treatment. The current study presented a case of advanced HCC beyond the Milan criteria who underwent LT and achieved a favorable outcome following PD-1 inhibitor combined with FOLFOX-HAIC therapy. Of note, due to treatment-induced tumor necrosis, precise post-treatment tumor size evaluation became challenging. To address this, circulating tumor DNA (ct-DNA) clearance was used as the LT criterion. After three cycles of Pembrolizumab and FOLFOX-HAIC therapy, the patient's serum ctDNA became undetectable and serum α-fetoprotein levels returned to normal. Magnetic resonance imaging results also revealed a significant reduction in liver tumor size post down-staging treatment. Subsequent to LT, serum ctDNA was monitored every two months, consistently yielding diminished results. There were no clinical signs of recurrence 19 months post-LT. These findings suggest that Pembrolizumab in combination with FOLFOX-HAIC may serve as a potential down-staging strategy prior to LT. In addition, ctDNA clearance may be considered a viable biomarker for LT eligibility.
RESUMEN
Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.