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BACKGROUND: Nivolumab monotherapy is the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) after failure of platinum-based chemotherapy without anti-PD-1 antibody. Fixed dosing with 240 mg every 2 weeks was approved initially, followed by fixed dosing with 480 mg every 4 weeks based on pharmacokinetics data. However, information on the comparative efficacy and safety of the two doses remains limited. METHODS: We compared progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and the incidence of adverse events (AEs) between the two doses in 117 patients who received second-line (n = 85) or later-line (n = 32) nivolumab monotherapy at our institution between January 2016 and December 2021. RESULTS: In the second-line group, patient characteristics for the 240 mg and 480 mg groups were as follows (240 mg vs. 480 mg): performance status (PS) 0/1/2 was 34/61/5% vs. 54/42/4%, and prior fluoropyrimidine plus platinum therapy (FP) was 81.3% vs. 42.3%. In the later-line group, the characteristics were: PS 0/1/2 was 28/60/12% vs. 14/86/0%, and prior FP was 60.0% vs. 42.8%. ORR was 11.9 vs. 24.0% in the second-line group (p = 0.19) and 0 vs. 14.3% in the later-line group (p = 0.22). Median PFS was 1.7 vs. 4.1 months on second-line (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.35-1.01, p = 0.056) and 1.4 vs. 1.8 months on later-line (HR 0.58, 95% CI 0.23-1.46, p = 0.25); AEs of any grade were observed in 58.3 vs. 69.7%, respectively. CONCLUSIONS: The efficacy and safety of the two doses of nivolumab monotherapy were comparable in patients with advanced ESCC.
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BACKGROUND: Nivolumab was approved for the treatment of advanced gastric cancer in 2017 in Japan. The aim of this study was to assess the impact of nivolumab in a real-world clinical setting. METHODS: This single-institutional retrospective study included patients with advanced gastric or esophagogastric junction adenocarcinoma and a history of first-line chemotherapy with platinum-based doublet or triplet regimens between 2010 and 2020. To assess the impact of nivolumab on survival, the patients were divided based on the year of nivolumab approval into a pre-2017 (2010-2016) group and a post-2017 (2017-2020) group. RESULTS: From a total of 1918 patients, 1093 were excluded. There were 533 patients in the pre-2017 group and 292 in the post-2017 group. Immune checkpoint inhibitors were used significantly more often in the post-2017 group than in the pre-2017 group (8.6% vs. 47.9%). Median overall survival was significantly longer in the post-2017 group (16.9 vs. 13.9 months; hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.63-0.90; p < 0.01). The proportion of patients transitioning to third-line treatment was higher in the post-2017 group than in the pre-2017 group (56.3% vs. 43.8%, p < 0.01). Median survival outcomes following progression on second-line treatment were significantly longer in the post-2017 group (4.3 vs. 3.2 months; HR 0.70, 95% CI 0.57-0.86; p < 0.01). CONCLUSION: The proportion of patients transitioning to third-line treatment and survival outcomes following progression on second-line treatment have improved since the approval of nivolumab. This drug might help to prolong overall survival in real-world practice.
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Inhibidores de Puntos de Control Inmunológico , Nivolumab , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Femenino , Anciano , Japón , Estudios Retrospectivos , Persona de Mediana Edad , Nivolumab/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Anciano de 80 o más Años , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Unión Esofagogástrica/patología , Resultado del TratamientoRESUMEN
The standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC) is chemoradiotherapy in western countries (based on the CROSS trial) and triplet chemotherapy in Japan (based on the JCOG1109 trial). Postoperative nivolumab has recently been shown to improve disease-free survival in resectable locally advanced esophageal cancer after preoperative chemoradiotherapy in patients who had residual pathological disease, based on the CheckMate 577 trial. Furthermore, preoperative immune checkpoint inhibitor-containing treatments have also been developed. The JCOG1804E trial is presently evaluating the safety and efficacy of preoperative nivolumab-containing chemotherapy for resectable locally advanced ESCC. This review discusses the treatment of resectable locally advanced ESCC and future perspectives on perioperative immune checkpoint inhibitor-containing treatments.
[Box: see text].
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BACKGROUND AND OBJECTIVE: Malignant ascites (MA) is common in patients with advanced cancer, and about 60% of patients with MA experience distressing symptoms. In addition, MA has been identified as a poor prognostic factor, therefore, making the management of MA an important issue. We aimed to review literature describing MA provide a narrative synthesis of relevant studies. METHODS: A literature search of articles published between 1971 and May 2023 was performed in PubMed, and Cochrane library using the words "ascites/malignant ascites" and the theme of each section. Authors independently selected the articles used and summarized. Finally, this manuscript was obtained consensus through discussed among all authors. KEY CONTENT AND FINDINGS: The pathophysiological mechanism of ascites formation involves increased vascular permeability and impaired fluid drainage through the lymphatic system, which explain the occurrence of peritoneal carcinomatosis, portal hypertension due to liver tumors, liver cirrhosis in the background of hepatocellular carcinoma, and Budd-Chiari syndrome caused by tumor occlusion of the hepatic vein. The efficacy and safety of various treatments and procedures have been investigated previously; however, no treatment guidelines have been established yet. Diuretics and paracentesis are often selected as the first lines of treatment. Intraperitoneal drug administration (catumaxomab, bevacizumab, aflibercept, hyperthermic intraperitoneal chemotherapy, triamcinolone), indwelling peritoneal catheters, peritoneovenous shunting, and cell-free and concentrated ascites reinfusion therapy are commonly used to manage refractory ascites. A new device for this purpose is alfapump, which transfers ascites fluid from the peritoneum into the urinary bladder. In addition, thoracic epidural analgesia may be effective for managing ascites-related symptoms. CONCLUSIONS: Despite these options, no standard treatment for MA has been established yet because few trials have been conducted in this area. There are many issues to be investigated, and future research and treatment development are expected.
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Ascitis , Neoplasias , Humanos , Ascitis/terapia , Ascitis/etiología , Ascitis/fisiopatología , Neoplasias/complicaciones , Neoplasias/terapiaRESUMEN
OBJECTIVES: The prognostic factors in patients with malignancy-related ascites (MA) have been poorly investigated. This study aimed to evaluate both the prognostic impact of MA on terminally ill patients with cancer and the prognostic factors in those with MA. METHODS: This was a post hoc analysis of a multicentre, prospective cohort study. Patients with advanced cancer admitted to palliative care units at 23 institutions and aged≥18 years were enrolled between January and December 2017. Overall survival (OS) was compared according to MA. A multivariate analysis was conducted to explore prognostic factors in patients with MA. RESULTS: Of 1896 eligible patients, gastrointestinal and hepatobiliary pancreatic cancers accounted for 42.5%. 568 (30.0%) of the total had MA. Patients with MA had significantly shorter OS than those without MA (median, 14 vs 22 days, respectively; HR, 1.55; 95% CI, 1.39 to 1.72; p<0.01). A multivariate analysis showed that MA was a poor prognostic factor (HR, 1.30; 95% CI, 1.13 to 1.50; p<0.01) and that among patients with MA, significant poor prognostic factors were liver metastasis, moderately to severely reduced oral intake, delirium, oedema, gastric cancer, high serum creatinine, high serum C reactive protein, high serum total bilirubin, dyspnoea and fatigue, while significant good prognostic factors were female sex, good performance status, high serum albumin and colorectal cancer. CONCLUSIONS: MA had a negative impact on survival in terminally ill patients with cancer. A multivariate analysis revealed several prognostic factors in patients with terminal cancer and MA.
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Neoplasias Hepáticas , Cuidados Paliativos , Humanos , Femenino , Masculino , Pronóstico , Estudios Prospectivos , Ascitis/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: While the efficacy of immune checkpoint inhibitors (ICIs) reportedly varies among metastatic sites and progression patterns (classified as systemic progression [SP] or mixed progression [MP]), the clinical efficacy of ICIs against gastric cancer remains unclear. The response to nivolumab depending on metastatic site and clinical outcomes according to progression pattern in patients with advanced gastric cancer was investigated retrospectively. METHODS: Seventy-four advanced gastric cancer patients with measurable lesions who received nivolumab monotherapy between 2015 and 2020 were enrolled. Progression-free survival (PFS), overall survival, response at each metastatic site, and clinical outcomes according to progression pattern were analyzed retrospectively. SP and MP were defined as progression in more than half of the lesions and progression in half or fewer of the lesions, respectively, in cases evaluated as progressive disease. RESULTS: Thirty-five (47%) and 27 (36%) patients had SP and MP, respectively, and 12 (16%) patients experienced no progression. The progression rates of target lesions in the lung (44%) and liver (57%) were significantly higher than that in the lymph nodes (18%) (lung vs. lymph node, p < 0.001; liver vs. lymph node, p = 0.03). Patients with MP had superior PFS to those with SP (median, 2.6 vs. 1.5 months; HR, 0.42; 95% CI, 0.23-0.76; p = 0.004). In MP group, patients with treatment beyond progression (TBP) with nivolumab had a trend of longer post-progression survival than those without TBP (median, 8.0 vs. 4.0 months; HR, 0.55; 95% CI, 0.23-1.29; p = 0.161). CONCLUSION: Patients with MP had a longer PFS than those with SP. Lung and liver metastases had a poorer response to an ICI than lymph node metastases.
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Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Gástricas , Humanos , Nivolumab/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Neoplasias Gástricas/tratamiento farmacológico , Estudios Retrospectivos , Antineoplásicos Inmunológicos/efectos adversosRESUMEN
BACKGROUND: The standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (LAESCC) in Japan is docetaxel, cisplatin (CDDP), and 5-fluorouracil. However, patients with renal or cardiac dysfunction and elderly patients are ineligible for a CDDP-containing regimen because of toxicities. Oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) therapy has less renal toxicity than CDDP-containing regimens and does not require hydration. However, there are limited data on preoperative FOLFOX therapy in these patients. METHODS: This retrospective study analyzed patients with resectable LAESCC who were aged ≥ 75 years or had renal or cardiac dysfunction and received preoperative FOLFOX between 2019 and 2021. FOLFOX was administered every 2 weeks for 3 or 4 cycles and was followed by surgery. Adverse events associated with chemotherapy, the complete resection (R0) rate, relative dose intensity (RDI), and histopathological response were evaluated. RESULTS: Thirty-five patients were eligible. Median age was 77 (range 65-89) years; 68.6% were aged ≥ 75 years, 74.3% had renal dysfunction, and 17.1% had cardiac dysfunction. The RDI was 70.2% and 87.1% for bolus and continuous intravenous 5-fluorouracil, respectively and 85.2% for oxaliplatin. The most common grade ≥ 3 adverse events were neutropenia (60.0%) and leucopenia (28.6%). Two patients (5.7%) had febrile neutropenia and grade 3 pneumonia. Thirty-one patients underwent surgery. The R0 resection rate was 87.1%, and there was no histopathological evidence of residual tumor in 16.1%. There were no treatment-related deaths. CONCLUSIONS: Preoperative FOLFOX had a manageable safety profile and showed favorable short-term efficacy in patients with resectable LAESCC who were ineligible for CDDP-containing treatment.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Cardiopatías , Anciano , Humanos , Anciano de 80 o más Años , Cisplatino/efectos adversos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/cirugía , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Oxaliplatino/uso terapéutico , Estudios Retrospectivos , Fluorouracilo/efectos adversos , Cardiopatías/inducido químicamente , Cardiopatías/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Esophageal cancer is the seventh most common cancer worldwide and continues to have a poor prognosis. Starting with the development of immune checkpoint inhibitors for patients with metastatic melanoma, many clinical trials have been conducted to evaluate the efficacy and safety of immune checkpoint inhibitors against various malignancies. Although few effective drugs are available for patients with advanced esophageal cancer, two immune checkpoint inhibitors, nivolumab and pembrolizumab, have been approved as second-line treatments for advanced esophageal squamous cell carcinoma. Recently, immune checkpoint inhibitors have shown promising results as post-operative therapies and first-line treatments for advanced esophageal cancer. Nivolumab has been approved as a post-operative therapy based on the CheckMate-577 trial, and nivolumab, ipilimumab and pembrolizumab have been approved as first-line treatments based on the CheckMate-648 trial and the KEYNOTE-590 trial. In addition, many trials of immune checkpoint inhibitors plus pre-operative treatment or definitive chemoradiotherapy are ongoing. The Japan Esophageal Oncology Group was established in 1978 and has conducted numerous clinical trials, most of which have examined multimodality treatments. In the era of immunotherapy, Japan Esophageal Oncology Group is conducting a clinical trial studying multimodality treatment with an immune checkpoint inhibitor. JCOG1804E (FRONTiER) is a phase I trial to evaluate the safety and efficacy of nivolumab plus pre-operative chemotherapy followed by surgery. These results might improve the clinical outcomes of esophageal cancer patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Anticuerpos Monoclonales/uso terapéutico , Ensayos Clínicos como Asunto , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Factores Inmunológicos , Inmunoterapia/métodos , Ipilimumab , Japón , Nivolumab/uso terapéuticoRESUMEN
An advanced small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome was resected, and we started capecitabine plus oxaliplatin (CapeOX) as adjuvant therapy. However, local recurrence was noted, and the tumor increased even after CapeOX plus bevacizumab and fluorouracil plus leucovorin plus irinotecan plus panitumumab (FOLFIRI plus panitumumab). Pembrolizumab was administered after confirming high-frequency microsatellite instability, and the tumor shrank markedly and remained shrunk for 20 months.
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Adenocarcinoma Mucinoso , Neoplasias Colorrectales , Síndrome de Peutz-Jeghers , Adenocarcinoma Mucinoso/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Camptotecina/uso terapéutico , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Recurrencia Local de Neoplasia , Síndrome de Peutz-Jeghers/tratamiento farmacológicoRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels. METHODS: We designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models. RESULTS: The change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group. CONCLUSIONS: The incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.
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Enfermedad del Hígado Graso no Alcohólico , gamma-Glutamiltransferasa , Alanina Transaminasa , Humanos , Pruebas de Función Hepática , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estudios RetrospectivosRESUMEN
We report a case of idiopathic hypereosinophilic syndrome (IHES) characterized by multiple liver mass lesions in an 82-year-old man. Numerous hypoechoic lesions were observed on ultrasonography and were mainly distributed in the S4, S6, and S7 segments. Plain computed tomography (CT) scans revealed low-density lesions. Dynamic CT images revealed arterial and portal vein branches passing through these lesions, with marginal areas enhanced during the arterial phase. The enhanced areas were extended during the portal venous phase. Contrast-enhanced ultrasonography (CEUS) images revealed enhanced vasculature in the early vascular phase. CEUS images obtained in the late vascular phase revealed enhanced areas containing microbubbles extended into the parenchyma; a prolonged enhancement pattern was observed. Kupffer-phase images revealed large portions of the lesion filled with microbubbles and a star-like defect at the center of the nodule. F18-2-fluoro-2-deoxyglucose (FDG) positron emission tomography/CT scans revealed intense FDG uptake by these lesions, which was similar to that by the segments S4, S6, and S7. Liver biopsy revealed diffused eosinophils infiltrated. The patient was closely followed up and was completely cured 11 weeks later without any treatment. This is a rare case of IHES with multiple liver mass lesions, which was well researched using multi-imaging equipment and cured without any treatment.