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PURPOSE: This study aimed to assess the viability of definitive chemoradiotherapy (dCRT) as an organ-preservation strategy for remarkable responders who were downstaged to stage IA after receiving induction chemotherapy for resectable esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: Chemotherapy-naïve patients with resectable ESCC (stage IB-III, Union for International Cancer Control, International Cancer Control seventh edition) were eligible for the study. All patients received 3 cycles of docetaxel, cisplatin, and 5-FU (DCF) therapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5-fluorouracil [5-FU] 750 mg/m2 on days 1-5, repeated every 3 weeks). Remarkable response was defined as a reduction in the tumor to T1, metastatic lymph nodes <1 cm on the short axis, and downstaging to stage IA after 3 cycles of DCF therapy. Remarkable responders then underwent dCRT, which included 2 courses of cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 on days 1 to 4, repeated every 4 weeks, along with 50.4 Gy of concurrent radiation therapy. The primary endpoint was 1-year progression-free survival in remarkable responders following DCF therapy and subsequent dCRT. Secondary endpoints included 3-year overall survival (OS) and esophagectomy-free survival. RESULTS: Of the 92 patients registered, 90 were analyzed. A remarkable response to 3 courses of DCF therapy was observed in 58.4% of patients. Among these responders, 89.8% achieved a complete response after dCRT. During the median follow-up period of 33 months (range, 1-85 months), the 1-year progression-free survival was 89.8% (95% confidence interval [CI], 77.2%-95.6%, primary endpoint), and the 3-year OS was 83.7%. The 3-year OS and esophagectomy-free survival rates in the analysis group were 74.1% and 45.3%, respectively. An 18F-fluorodeoxyglucose-positron emission tomography response after 2 courses of DCF therapy was significantly associated with OS (P = .0049). CONCLUSIONS: In patients with resectable ESCC, dCRT for remarkable responders downstaging to stage IA after induction chemotherapy with 3 courses of DCF therapy is a feasible treatment option and provides an optimizing organ-preservation strategy of chemotherapy-based selection.
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BACKGROUND: Luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, potentially exerts pleiotropic effects on the liver. However, the sufficient evidence is still lacking. We aimed to investigate the effects of luseogliflozin on hepatic steatosis, fibrosis, and cardiometabolic risk factors in diabetic patients by a pooled meta-analysis. METHODS: In this pooled meta-analysis, we enrolled diabetic patients who participated in phase III clinical trials of luseogliflozin (luseogliflozin group n = 302, placebo group n = 191). The primary outcomes were changes in fatty liver index (FLI) and Hepamet fibrosis score (HFS) after 24 weeks. The secondary outcomes were changes in cardiometabolic risk factors after 24 weeks. Statistical analysis was performed using propensity scoring analysis by the inverse probability of treatment weighting method. RESULTS: Primary outcomes: Luseogliflozin significantly decreased FLI compared to placebo after 24 weeks (adjusted coefficient - 5.423, 95%CI - 8.760 to - 2.086, P = 0.0016). There was no significant difference in changes in HFS between the two groups. However, luseogliflozin significantly decreased HFS compared to placebo in diabetic patients with ALT > 30 U/L (adjusted coefficient - 0.039, 95%CI - 0.077 to - 0.001, P = 0.0438) and with FIB-4 index > 1.3 (adjusted coefficient - 0.0453, 95%CI - 0.075 to - 0.016, P = 0.0026). Secondary outcom8es: Luseogliflozin significantly decreased HbA1c level, HOMA-IR value, BMI, and uric acids level, and increased HDL cholesterol level compared to placebo. CONCLUSIONS: This pooled meta-analysis demonstrated that 24-week treatment with luseogliflozin improved hepatic steatosis and fibrosis indexes in diabetic patients, especially those with liver injury. Furthermore, luseogliflozin improved various cardiometabolic risk factors. Thus, luseogliflozin may be useful for improving MASLD in diabetic patients.
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PURPOSE: Non-invasive reduction in patients with incarcerated obturator hernias is an emergency surgery alternative. There are two non-invasive reduction types: manual and ultrasonographic (ultrasound-guided and ultrasound-assisted reduction). However, the impact of ultrasound guidance on manual reduction has not been adequately evaluated. We aimed to compare non-invasive ultrasound reduction with manual reduction in patients with incarcerated obturator hernias. METHODS: We searched MEDLINE, Cochrane Central Library, Embase, Ichushi Web, ClinicalTrial.gov, and ICTRP for relevant studies. The primary outcomes were success and bowel resection rates. We performed a subgroup analysis between ultrasound-guided and ultrasound-assisted reductions. This study was registered in PROSPERO (CRD 42,024,498,295). RESULTS: We included six studies (112 patients, including 12 from our cohort). The success rate was 78% (69 of 88 cases) with ultrasonographic reduction and 33% (8 of 24 cases) with manual reduction. The success rate was higher with ultrasonographic than with manual reduction. Subgroup analysis revealed no significant difference between ultrasonography-assisted (76%) and ultrasonography-guided (80%) reductions (p = 0.60). Non-invasive reductions were predominantly successful within 72 h of onset, although durations extended up to 216 h in one case. Among the successful reduction cases, emergency surgery and bowel resection were necessary in two cases after 72 h from onset. Bowel resection was required in 48% (12 of 25), where the non-invasive reduction was unsuccessful within 72 h of confirmed onset. CONCLUSIONS: Ultrasonographic reduction can be a primary treatment option for patients with obturator hernias within 72 h of onset by emergency physicians and surgeons on call. Future prospective studies are needed to evaluate ultrasonographic reduction's impact.
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Cancer cachexia causes anorexia and metabolic disorders, eventually leading to sarcopenia, which in turn contributes to the development of functional disabilities. Although anamorelin hydrochloride tablets are marketed to treat cancer cachexia, their efficacy varies significantly among patients. Here, we investigated the efficacy of anamorelin and the factors associated with weight gain. The factors that contributed to weight gain in patients before starting anamorelin were as follows: the patients' disease stage had not progressed to refractory cachexia based on the cancer cachexia classification of the European Palliative Care Research Collaborative; the patients had received fewer lines of anticancer treatment at the start of oral administration of anamorelin; and the patients had not met all the criteria for starting treatment with anamorelin, namely, C-reactive protein level >0.5 mg/dL, hemoglobin level <12 g/dL, and albumin level <3.2 g/dL. These results suggest that early administration of anamorelin hydrochloride tablets may increase the response rate when cancer cachexia is diagnosed.
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Caquexia , Neoplasias , Aumento de Peso , Humanos , Caquexia/tratamiento farmacológico , Caquexia/etiología , Neoplasias/complicaciones , Masculino , Femenino , Anciano , Persona de Mediana Edad , Aumento de Peso/efectos de los fármacos , Anciano de 80 o más Años , Glicina/análogos & derivados , Glicina/uso terapéutico , Glicina/administración & dosificación , Hidrazinas/uso terapéutico , Hidrazinas/administración & dosificación , OligopéptidosRESUMEN
BACKGROUND: The real-world efficacy, feasibility, and prognostic factors of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer are not fully established. METHODS: This multi-institutional retrospective cohort study evaluated 71 consecutive patients treated with immune-checkpoint inhibitor combination therapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, safety, and long-term survival. RESULTS: In patients with measurable lesions, the response rate was 58%, and the disease control rate for all enrolled patients was 80%. Five patients (7.0%) underwent successful conversion surgery. Grade 3 or higher immune-related adverse events occurred in 13% of patients, and one patient (1.4%) died due to cholangitis. Median progression-free survival was 9.7 (95% confidence interval: 6.5-not reached). C-reactive protein levels and performance status were identified as significant predictors of progression-free survival through Cox proportional hazards analysis. CONCLUSIONS: Immune-checkpoint inhibitor combination therapy for esophageal cancer demonstrated comparable tumor response, safety, and long-term survival to previous randomized clinical trials. Patients with good performance status and low C-reactive protein levels may be suitable candidates for this treatment.
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Neoplasias Esofágicas , Inhibidores de Puntos de Control Inmunológico , Humanos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Adulto , Supervivencia sin Progresión , Proteína C-Reactiva/análisisRESUMEN
The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.
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Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Ratones , Animales , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/patología , Ratones Endogámicos C57BL , Epiplón/patología , Nervio Vago/cirugía , Nervio Vago/patologíaRESUMEN
The spleen is a key source of circulating and tumor-infiltrating immune cells. However, the effect of splenectomy on tumor growth remains unclear. At 3 weeks after splenectomy, we subcutaneously injected LuM1 cells into BALB/c mice and evaluated the growth of primary tumors and lung metastases at 4 weeks after tumor inoculation. In addition, we examined the phenotypes of immune cells in peripheral blood by using flow cytometry and in tumor tissue by using multiplex immunohistochemistry. The growth of primary tumors was reduced in splenectomized mice compared with the sham-operated group. Conversely, splenectomized mice had more lung metastases. Splenectomized mice had fewer CD11b+cells, especially monocytic MDSCs (CD11b+Gr-1neg-lowLy6chigh), and NK cells (CD49b+CD335+). The proportion of NK cells was inversely correlated with the number of lung metastases. In splenectomized mice, the density of CD3+ and granzyme B+ CD8+ T cells was increased, with fewer M2-type macrophages in primary tumors, but NK cells were decreased markedly in lung. Splenectomy concurrently enhances T cell-mediated acquired immunity by reducing the number of monocytic MDSCs and suppresses innate immunity by decreasing the number of NK cells. Splenectomy has opposite effects on primary and metastatic lesions through differential regulation on these two immune systems.
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Neoplasias del Colon , Neoplasias Pulmonares , Ratones , Animales , Esplenectomía , Linfocitos T CD8-positivos , Células Asesinas Naturales , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neoplasias del Colon/patologíaRESUMEN
Background: Adjuvant nivolumab therapy has become the standard therapy for patients with localized advanced esophageal cancer with non-pathological complete response after neoadjuvant chemoradiotherapy followed by curative surgery. However, the necessity of this therapy for patients after neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen followed by surgery is unclear, and the prognosis of grouping based on the presence or absence of pathological tumor and lymph node findings has not been analyzed. Therefore, our study aimed to address these questions. Methods: This retrospective cohort study included patients with cT1N1-3M0 and cT2-3N0-3M0 esophageal cancer according to the Japanese Classification of Esophageal Cancer, 11th edition, who received NAC with DCF followed by curative surgery between 2008 and 2020 at Jichi Medical University Hospital. We divided patients with ypT0-3N0-3M0 into four histological groups, namely ypT0N0, ypT+N0, ypT0N+, and ypT+N+, and we evaluated overall survival as the primary outcome and the prognostic relationship of lymph node metastasis as the secondary outcome. Results: A total of 101 patients were included in this study. Kaplan-Meier analysis showed that the curves of the ypT0N0 and ypT+N0 groups were almost identical, while they differed from the other two groups. The hazard ratio of ypN+ was 4.44 (95% confidence interval: 2.03-9.71; P<0.001). Conclusions: The prognosis of the ypT+N0 group after NAC with DCF followed by surgery was similar to that of pathological complete remission. Grouping patients according to pathological lymph node status is a reasonable predictor of prognosis.
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BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.
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Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Cisplatino , Neoplasias Gástricas/patología , Paclitaxel , Neoplasias Peritoneales/secundario , Protocolos de Quimioterapia Combinada AntineoplásicaAsunto(s)
Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Cisplatino/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Paclitaxel , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Peritoneo/patología , Inyecciones Intraperitoneales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer. MATERIAL AND METHODS: In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model. RESULTS: The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark. CONCLUSION: As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time.
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Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Neoplasias Colorrectales , Humanos , Resultado del Tratamiento , Gemcitabina , Cisplatino/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológicoRESUMEN
The prognosis of patients with peritoneal metastases from pancreatic cancer is poor, largely due to massive ascites, which precludes systemic treatment. Two patients with a poor performance status and malignant ascites were treated with cell-free and concentrated ascites reinfusion therapy followed by combined chemotherapy with intraperitoneal paclitaxel, intravenous gemcitabine, and nab-paclitaxel. These patients achieved a survival of 19 and 36 weeks with a relatively good quality of life. Combined intraperitoneal paclitaxel and systemic chemotherapy may provide effective palliative management for some patients with peritoneal metastases from pancreatic cancer.
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The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno's concordance index was 0.661 (95% confidence interval [CI] 0.629-0.696) in the training set and 0.640 (95% CI 0.566-0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians' prognosis-based decision-making.
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Neoplasias del Sistema Biliar , Nomogramas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gemcitabina , Desoxicitidina , Pronóstico , Cisplatino/uso terapéutico , Neoplasias del Sistema Biliar/patologíaRESUMEN
Introduction: The abscopal effect (AE) is a phenomenon, in which radiotherapy exerts an antitumour effect on distant lesions outside the primary irradiated area. Although immune checkpoint inhibitors have been widely studied for their potential to enhance the AE and improve patient outcomes, findings in cases of head and neck cancers remain limited. Case Presentation: We report the case of a 72-year-old man who experienced lung oligoprogression during nivolumab treatment for metastatic hypopharyngeal cancer. Stereotactic body radiotherapy (SBRT) was administered to one of the lung lesions, after which both irradiated and nonirradiated lesions regressed. Upon an 18-month follow-up period after SBRT, the patient showed no disease progression or toxicity, and continued receiving nivolumab therapy. Conclusion: The intent behind presenting this case report was to contribute to the accumulation of evidence regarding the AE in cases of head and neck cancer.
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Cutaneous metastasis from malignant tumors can cause symptoms such as exudates, bleeding, and pain, which remarkably reduce patient's quality of life. Herein, we report a case in which radiation therapy using the Quad Shot regimen was effective in the treatment of cutaneous metastasis from parotid gland cancer.
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BACKGROUND: The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial. METHODS: This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m2 is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110). RESULTS: We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies. CONCLUSION: Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.
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Neoplasias Colorrectales , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Bevacizumab/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Colorrectales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
Esophageal neuroendocrine carcinoma (E-NEC) is an aggressive disease with a poor prognosis. The present study aimed to assess the role of surgery in the treatment of patients with resectable E-NEC, and identify a microRNA (miRNA/miR) signature in association with positive postoperative outcomes. Between February 2017 and August 2019, 36 patients with E-NEC who underwent curative surgery at the Japan Neuroendocrine Tumor Society partner hospitals were enrolled in the study. A total of 16 (44.4%) patients achieved disease-free survival (non-relapse group), whereas 20 (55.6%) patients developed tumor relapse (relapse group) during the median follow-up time of 36.5 months (range, 1-242) after surgery with a 5-year overall survival rate of 100 and 10.8%, respectively (P<0.01). No clinicopathological parameters, such as histological type or TNM staging, were associated with tumor relapse. Microarray analysis of 2,630 miRNAs in 11 patients with sufficient quality RNA revealed 12 miRNAs (miR-1260a, -1260b, -1246, -4284, -612, -1249-3p, -296-5p, -575, -6805-3p, -12136, -6822-5p and -4454) that were differentially expressed between the relapse (n=6) and non-relapse (n=5) groups. Furthermore, the top three miRNAs (miR-1246, -1260a and -1260b) were associated with overall survival (P<0.01). These results demonstrated that surgery-based multidisciplinary treatment is effective in a distinct subpopulation of limited stage E-NEC. A specific miRNA gene set is suggested to be associated with treatment outcome.
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OBJECTIVE: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment. METHODS: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association. RESULTS: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival. CONCLUSIONS: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy.
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Proteína C-Reactiva , Neoplasias Pancreáticas , Humanos , Proteína C-Reactiva/metabolismo , Quimioterapia de Inducción , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
QUAD SHOT is an ultra-hypofractionated radiotherapy (RT) technique that prescribes 14.0-14.8 Gy over 2 days. Although this technique has already gained some status as an effective palliative treatment for inoperable head and neck cancer (HNC), its application in other situations has not been given much consideration. Herein, we report a case of a 62-year-old woman who received preoperative QUAD SHOT therapy for poorly differentiated parotid carcinoma. In this case, after two courses of QUAD SHOT plus a standard chemotherapy regimen with pembrolizumab, the patient's inoperable, bulky tumor shrank dramatically and became operable. Best of all, while adequate therapeutic effects were achieved, the patient's time commitment and physical exertion were limited. RT during this period consisted of only eight fractions over 4 days. According to previous reports, the response rate for QUAD SHOT is sufficiently high, and the rate of serious adverse events is quite low. This case asks the question of whether the indications for QUAD SHOT irradiation can be expanded as one of the preoperative interventions undertaken by HNC surgeons to achieve conversion surgery.
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Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR-29b levels in peritoneal exosomes were markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked whether the replacement of miR-29b can affect the development of PM in a murine model. UE6E7T-12, human bone marrow-derived mesenchymal stem cells (BMSCs), were transfected with miR-29b-integrating recombinant lentiviral vector and sEV were isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR-29b compared with negative controls. Treatment with transforming growth factor-ß1 decreased the expression of E-cadherin and calretinin with increased expression of vimentin and fibronectin on human omental tissue-derived mesothelial cells (HPMCs). However, the effects were totally abrogated by adding miR-29b-rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p < 0.005, n = 6) and 70% (p < 0.005, n = 6), respectively, and inhibited adhesion of NUGC-4 and MKN45 to HPMCs by 90% (p < 0.0001, n = 5) and 77% (p < 0.0001, n = 5), respectively. MicroRNA-29b-rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p < 0.05, n = 6) and the omentum (p < 0.05, n = 6). Bone marrow mesenchymal stem cell-derived sEV are a useful carrier for IP administration of miR-29b, which can suppress the development of PM of gastric cancer.