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The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently practiced requires a wide variety of beam quality assessments to ensure that RBE dose errors are maintained within 5%. However, the necessity of maintaining a constant beam dose rate has not been fully discussed. We therefore clarified the effect of different physical dose rates of the accelerator BNCT on biological effects. SAS and A172 cells exposed to 10B-boronophenylalanine were irradiated using a neutron beam (normal operating current, 100 µA) at the Aomori Quantum Science Center. Thermal neutron flux was attenuated to 50.0 ± 0.96% under 50 µA irradiation compared to that under 100 µA irradiation. Cells were given physical doses of 1.67 and 3.36 Gy at 30 and 60 mC, respectively, and survival was significantly increased after 50 µA irradiation for both cell types (p = 0.0052 for SAS; p = 0.046 for A172, for 60 mC). Differences in accelerator BNCT beam dose rates have non-negligible effects on biological effects. Dose rate fluctuations and differences should not be easily permitted to obtain consistent biological effects.
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BACKGROUND: Accelerated tumor growth during immunotherapy in pre-existing measurable lesions, hyperprogressive disease (HPD), has been reported. However, progression of non-measurable lesions and new lesions are frequently observed in patients with advanced gastric cancer (AGC). METHODS: This retrospective study involved AGC patients at 24 Japanese institutions who had measurable lesions and received nivolumab after ≥ 2 lines of chemotherapy. HPD was defined as a ≥ two-fold increase in the tumor growth rate of measurable lesions. The pattern of disease progression was classified according to new lesions in different organs and ascites appeared/increase of ascites. RESULTS: Of 245 patients, 147 (60.0%) showed progressive disease (PD) as the best response and 41 (16.7%) showed HPD during nivolumab monotherapy. There was no significant difference in overall survival (OS) between patients with HPD and those with PD other than HPD (median OS 5.0 vs 4.8 months; hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.6-1.5; p = 1.0). Fifty-three patients developed new lesions in different organs and 58 had appearance/increase of ascites; these patients showed shorter OS than those without each of these features (median OS 3.3 vs 7.1 months, HR 1.8, 95% CI 1.2-2.7, p = 0.0031 for new lesions, and 3.0 vs 7.8 months, HR 2.6, 95% CI 1.8-3.8, p < 0.0001 for ascites). Thirty-one patients who had both features showed the worst prognosis (median OS 2.6 months). CONCLUSIONS: New lesions in different organs and appearance/increase of ascites, rather than the original definition of HPD, are the patterns of disease progression associated with poor prognosis in AGC patients receiving nivolumab whose best response was PD.
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Nivolumab , Neoplasias Gástricas , Humanos , Nivolumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Estudios Retrospectivos , Japón , Ascitis , Pronóstico , Progresión de la EnfermedadRESUMEN
Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a subtype for which new drugs and specific treatment strategies should be developed. Trastuzumab deruxtecan (T-DXd) is a novel HER2-targeted antibody-drug conjugate containing topoisomerase I inhibitor as a payload. In the randomized phase 2 study (DESTINY-Gastric01) for HER2-positive advanced gastric or gastroesophageal junction cancer (AGC), patients treated with T-DXd showed a significantly higher response rate compared with the chemotherapy of physician's choice, associated with remarkably prolonged progression-free and overall survival. T-DXd also exhibits anti-tumor activity to HER2-negative tumor cells close to HER2-positive cells (so-called bystander killing effect). T-DXd was effective even for HER2-low expressing breast and gastric cancer in several clinical studies. Taking advantage of these strong points and synergism with other cytotoxic, molecular-targeted and immunological agents, it is expected that T-DXd will bring further progression in treatment both for strongly and weakly HER2 positive AGC in various treatment settings including perioperative chemotherapy.
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Camptotecina/análogos & derivados , Inmunoconjugados/uso terapéutico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/uso terapéutico , Camptotecina/administración & dosificación , Camptotecina/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Inmunoconjugados/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Trastuzumab/administración & dosificaciónRESUMEN
Background Ramucirumab (RAM) plus solvent-based (sb)-paclitaxel (PTX) is the standard second-line chemotherapy for advanced gastric cancer (AGC). The subset analysis of the ABSOLUTE trial, which confirmed non-inferiority of weekly nanoparticle albumin-bound (nab)-PTX to weekly sb-PTX, suggested that nab-PTX might have better efficacy than sb-PTX in patients with peritoneal metastasis. We retrospectively evaluated the efficacy and safety of RAM plus sb-PTX and nab-PTX in patients with peritoneal metastasis of AGC. Methods AGC patients who received RAM plus sb-PTX or nab-PTX as second-line chemotherapy from June 2015 to February 2019 were included in the study. Overall survival (OS), progression-free survival (PFS), response rate, and safety were assessed. Results A total of 128 patients were included in this study (93 in the RAM plus sb-PTX group and 35 in the RAM plus nab-PTX group). PFS was 4.1 months in the RAM plus sb-PTX group and 4.6 months in the RAM plus nab-PTX group (HR 0.90; 95%CI 0.58-1.41, p = 0.643). OS was 8.9 months in the RAM plus sb-PTX group and 11.4 months in the RAM plus nab-PTX group (HR 0.95; 95%CI 0.56-1.62, p = 0.847). A total of 62 and 31 patients had peritoneal metastasis in the RAM plus sb-PTX and the RAM plus nab-PTX groups, respectively. RAM plus nab-PTX showed a slightly longer survival compared to RAM plus sb-PTX in patients with peritoneal metastasis (PFS 5.8 vs 3.5 months, HR 0.66; 95% CI 0.40-1.10, p = 0.109). Conclusion This study suggests that RAM plus nab-PTX might be a more effective treatment for peritoneal metastasis of AGC.
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Albúminas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Albúminas/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia , Resultado del Tratamiento , RamucirumabRESUMEN
BACKGROUND: Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival. METHODS: The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. RESULTS: Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2-3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival. CONCLUSIONS: Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.
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Neoplasias Pulmonares/secundario , Radiocirugia/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. In this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab. METHODS: The subjects of this study were AGC patients received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups. RESULTS: Of the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3-407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p < 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p < 0.001). Multivariate analysis demonstrated that number of metastatic sites ≥2 (HR = 2.15; 95% CI, 1.02 to 4.54), high ALP level (HR = 2.50; 95% CI, 1.27 to 4.54), and absence of irAEs (HR = 9.54, 95% CI, 3.34 to 27.30 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). There were no grade 4 or 5 adverse events related to nivolumab. CONCLUSIONS: Development of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.
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Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Inmunoterapia/efectos adversos , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Insuficiencia Suprarrenal/etiología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/farmacología , Diarrea/etiología , Femenino , Estudios de Seguimiento , Humanos , Hiperglucemia/etiología , Masculino , Persona de Mediana Edad , Nivolumab/farmacología , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Laparoscopic and endoscopic cooperative surgery (LECS) was performed for the local resection of gastrointestinal stromal tumors (GIST). LECS enables less resection of the lesion area and preserves function. Furthermore, LECS can be safely performed and independent of tumor location. However, LECS is not usually used for cases involving gastric carcinoma because it may seed tumor cells into the peritoneal cavity when the gastric wall is perforated. Here, we report seven cases of LECS for intra-mucosal gastric carcinoma, which were difficult to carry out by endoscopic submucosal dissection (ESD) because of ulcer scars. METHODS: We performed LECS (classical LECS and inverted LECS) in seven cases of intra-mucosal gastric carcinoma. All cases had ulcer scars beside the tumor. LECS was chosen because ESD was thought to be difficult because of the ulcer scars. We only selected cases in which the patients did not prefer gastrectomy and endoscopic examination was indicative of intra-mucosal gastric carcinoma. RESULTS: In all cases, LECS was performed without severe complications including postoperative stenosis. Histopathology findings proved that the tumors were intra-mucosal carcinoma and had been resected completely. Furthermore, there were ulcer scars (Ul IIIs-IVs) beside the tumor. Currently, dissemination and recurrence have not been apparent. CONCLUSIONS: LECS for intra-mucosal gastric carcinoma is an efficient procedure, but strict observation is necessary because of the possibility of peritoneal dissemination. Results suggest that LECS is likely to be effective for cases involving intra-mucosal gastric carcinoma that are difficult to treat by ESD due to ulcer scars.
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Cicatriz/cirugía , Resección Endoscópica de la Mucosa/métodos , Gastrectomía/métodos , Mucosa Gástrica/cirugía , Laparoscopía/métodos , Neoplasias Gástricas/cirugía , Úlcera/cirugía , Anciano , Anciano de 80 o más Años , Cicatriz/patología , Estudios de Seguimiento , Mucosa Gástrica/patología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Úlcera/patologíaRESUMEN
A 72-year-old man was diagnosed with acute myeloid leukemia and advanced esophageal cancer(cT3N3M1, clinical Stage IV, high-moderately differentiated squamous cell carcinoma). He was started on remission induction chemotherapy and postremission therapy provided according to the Japan Adult Leukemia Study Group's AML201 protocols. His acute myeloid leukemia showed a complete response. After that, he was administered radiotherapy for esophageal cancer and showed a partial response. One year after treatment, he developed a local recurrence of esophageal cancer. A salvage operation was performed at another hospital, and his postoperative course was uneventful. A case of acute myeloid leukemia with advanced esophageal cancer is rare and has a poor prognosis, but we could improve the prognosis and quality of life.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias Esofágicas/diagnóstico por imagen , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasias Primarias Múltiples/terapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagen , Leucemia Mieloide Aguda/patología , Masculino , Neoplasias Primarias Múltiples/diagnóstico por imagen , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study was to investigate the prognostic role of the pretreatment neutrophil-to-lymphocyte ratio (NLR) as a predictive marker prior to treatment of cervical cancer with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). METHODS: Fifty-six patients with squamous cell carcinoma (SCC) of the uterine cervix who underwent RT or CCRT from 2005-2013 at the Hirosaki University Hospital were retrospectively identified using electronic databases. Patients were divided into a high NLR group (≥2.5) and a low NLR group (<2.5). The efficacy of RT and CCRT in the two groups was compared. RESULT: Of the 56 patients, 35 were in the high NLR group and 21 were in the low NLR group. In comparison to a high NLR, a low NLR was significantly associated with a complete response (P < 0.001). When cancer was divided into stages I/II and III/IV, patients with a low NLR had a significantly better therapeutic outcome than those with a high NLR (P < 0.05). Multivariate analysis showed that only the NLR was a significant prognostic factor for progression-free survival (PFS) and overall survival (OS). Patients with a high NLR had significantly shorter PFS and OS than those with a low NLR. CONCLUSION: Results showed that a low NLR before treatment could predict a good response to RT or CCRT at all stages of uterine cervical cancer. The NLR may be a promising parameter on which to base the choice of a therapeutic strategy to treat SCC of the uterine cervix.
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Carcinoma de Células Escamosas/terapia , Recuento de Leucocitos , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/radioterapia , Quimioradioterapia , Terapia Combinada , Femenino , Humanos , Linfocitos , Persona de Mediana Edad , Neutrófilos , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
BACKGROUND: This multi-institutional study was conducted to clarify the clinicopathological features of squamous cell carcinomas of the vulva. METHODS: The medical records of vulvar cancer patients treated between 2002 and 2012 were retrospectively reviewed following approval by the Institutional Review Board of each institution. RESULTS: One hundred and eleven patients with vulvar malignancies were included. Of these, 63 patients had squamous cell carcinoma (57 %). Initial treatment was surgery, radiation therapy (RT), and concurrent chemoradiotherapy (CCRT) in 34 (54 %), 15 (24 %), and 11 (17 %) patients, respectively. Nineteen, 11, 26, and 7 patients had stage I, II, III, and IV disease, respectively. Of the 34 patients who had surgical treatment, 50 % had stage I disease, while 74 % of those who received CCRT had stage III or IV disease. Complete response (CR) rates for the surgery, RT, and CCRT groups were 73, 60, and 64 %, respectively. The 5-year survival rates for stage I/II and III/IV disease were 64 and 39 %, respectively (P = 0.019). The 5-year survival rates for the surgery, RT, and CCRT groups were 53, 38, and 50 %, respectively, and the prognosis of patients treated with surgery or CCRT was significantly better than that of patients who received RT (P < 0.05). In multivariate analysis, clinical response to initial treatment was an independent prognostic factor (P < 0.001). CONCLUSIONS: Although many patients had advanced-stage disease in the CCRT group, the therapeutic outcome for the surgery and CCRT groups was similar. Thus, CCRT may be a promising treatment for squamous cell carcinoma of the vulva.
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Carcinoma de Células Escamosas/patología , Neoplasias de la Vulva/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/terapia , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Vulva/terapia , Adulto JovenRESUMEN
BACKGROUND: To date, the different treatment modalities for high-risk prostate cancer (Pca) have not been compared in any sufficiently large-scale, prospective, randomized clinical trial. We used propensity-score matching analysis to compare the oncological outcomes of high-risk prostate cancer between patients treated with radical prostatectomy (RP) and those treated with radiation therapy (RT). METHODS: We studied 216 patients who received neoadjuvant therapy followed by RP (RP cohort) and 81 patients who received neoadjuvant androgen-deprivation therapy (ADT) followed by RT (RT cohort). The RP cohort received a luteinizing hormone-releasing hormone agonist and estramustine phosphate (280 mg/day) for 6 months prior to RP. The RT cohort received ADT for at least 6 months prior to RT using a 3-dimensional conformal radiotherapy technique. The total radiation dose was 70 to 76 Gy administered at 2 Gy/fraction. RESULTS: Propensity-score matching identified 78 matched pairs of patients. The 3-year overall survival rates were 98.3% and 92.1% in the RP and RT groups, respectively (P=0.156). The 3-year biochemical recurrence-free survival rates were 86.4% and 89.4% in the RP and RT groups, respectively (P=0.878). CONCLUSIONS: Our study findings may suggest almost identical cancer control of RP and RT with appropriate neoadjuvant therapy in high-risk Pca. Therefore, issues of health-related quality of life may have an important impact on decision making in treatment of high-risk Pca.
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Adenocarcinoma/terapia , Antineoplásicos Hormonales/administración & dosificación , Estramustina/administración & dosificación , Hormona Liberadora de Gonadotropina/administración & dosificación , Terapia Neoadyuvante , Prostatectomía , Neoplasias de la Próstata/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Terapia Combinada , Estudios de Seguimiento , Hormona Liberadora de Gonadotropina/agonistas , Humanos , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Puntaje de Propensión , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Calidad de Vida , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The generality of a model for predicting tumor control probability from in vitro clonogenic survival considering of cancer stem-like cells, the so-called integrated microdosimetric-kinetic model, is presented by comparing the model to public data on stereotactic body radiation therapy for non-small cell lung cancer cells.
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Volumetric-modulated arc therapy (VMAT) is a radiotherapy technique used to treat patients with localized prostate cancer, which is frequently associated with acute adverse events (AEs) that can affect subsequent treatment. Notably, the radiation dose of VMAT can be tailored to each patient. In the present study, a retrospective analysis was performed to predict acute AEs in response to a therapeutic high radiation dose rate based on urinary metabolomic molecules, which are easily collected as noninvasive biosamples. Urine samples from 11 patients with prostate cancer who were treated with VMAT (76 Gy/38 fractions) were collected. The study found that seven patients (~64%) exhibited genitourinary toxicity (Grade 1) and four patients had no AEs. A total of 630 urinary metabolites were then analyzed using a mass spectrometer (QTRAP6500+; AB SCIEX), and 234 relevant molecules for biological and clinical applications were extracted from the absolute quantified metabolite values using the MetaboINDICATOR tool. In the Grade 1 acute AE group, there was a significant negative correlation (rs=-0.297, P<0.05) between the number of VMAT fractions and total phospholipase A2 activity in the urine. Additionally, patients with Grade 1 AEs exhibited a decrease in PC aa C40:1, a phospholipid. These findings suggested that specific lipids found in urinary metabolites may serve as predictive biomarkers for acute AEs in response to external radiotherapy.
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Epignathus is an extremely rare teratoma found in the oral cavity or oropharyngeal region of newborns, whose pathogenesis is poorly understood. We describe a giant epignathus arising from the oropharynx in a newborn. The giant tumor completely obstructed the airway of the newborn resulting in death. Histological and radiological examination of the tumor reveals the presence of a remarkably well-developed skeleton of the head and neck. A row of teeth, the axis and atlas, thyroid and salivary glands, trachea, and cerebral tissue are all detected within the tumor. These findings suggest that the epignathus is fetus-in-fetu which is considered a type 0 germ cell tumor in accordance with current literature.
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Neoplasias de la Boca , Teratoma , Humanos , Recién Nacido , Neoplasias de la Boca/patología , Teratoma/diagnóstico , Teratoma/cirugía , Teratoma/patología , Glándula Tiroides/patología , Esqueleto/patologíaRESUMEN
The aim of this study was to investigate the effectiveness of brain natriuretic peptide (BNP) as a predictor of radiological effects on the heart. A total of 41 patients with esophageal cancer who underwent chemoradiotherapy (CRT) were retrospectively investigated. The BNP levels were measured on the first day of CRT (pre-CRT) and the last day of CRT (post-CRT), and the median concentration of BNP and dosimetric parameters of the heart were calculated. The change ratio of BNP was calculated as follows: [(BNP post-CRT) - (BNP pre-CRT)]/(BNP pre-CRT). The comparison of BNP pre-CRT with post-CRT was performed using a Wilcoxon signed-rank test. The relationship between dosimetric parameters and change ratio was analyzed using Spearman's correlation coefficient. The median levels of BNP of pre-CRT and post-CRT were 10 and 22 pg/ml, respectively, and the difference was statistically significant (P<0.0001). Significant correlations (all P<0.05) were observed between the change ratio and mean dose, V5, V10, V20, and V30. Of the cohort, 14 patients developed acute-to-subacute cardiac events, such as pericardial effusion, cardiomegaly, acute exacerbation of chronic heart failure, and a decreased ejection fraction. The change ratios of BNP, V5, V10, V20, and V30 were significantly higher in patients who experienced cardiac events compared with those who did not. The results of this study showed that BNP measurement, particularly the change ratio of BNP pre- and post-CRT, may be a useful cardiac event predictor in addition to dosimetric parameters.
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BACKGROUND: Curative effects of stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) have been evaluated using various biophysical models. Because such model parameters are empirically determined based on clinical experience, there is a large gap between in vitro and clinical studies. In this study, considering the heterogeneous cell population, we performed a translational study to realize the possible linkage based on a modeling approach. METHODS: We modeled cell-killing and tumor control probability (TCP) considering two populations: progeny and cancer stem-like cells. The model parameters were determined from in vitro survival data of A549 and EBC-1 cells. Based on the cellular parameters, we predicted TCP and compared it with the corresponding clinical data from 553 patients collected at Hirosaki University Hospital. RESULTS: Using an all-in-one developed model, the so-called integrated microdosimetric-kinetic (IMK) model, we successfully reproduced both in vitro survival after acute irradiation and the 3-year TCP with various fractionation schemes (6-10 Gy per fraction). From the conventional prediction without considering cancer stem cells (CSCs), this study revealed that radioresistant CSCs play a key role in the linkage between in vitro and clinical outcomes. CONCLUSIONS: This modeling study provides a possible generalized biophysical model that enables precise estimation of SBRT worldwide.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radiocirugia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Fraccionamiento de la Dosis de Radiación , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
Apatinib is known to be a highly selective vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with anti-angiogenic and anti-tumor properties. In a phase III study, the objective response rate to apatinib was low. It remains unclear why the effectivity of apatinib varies among patients and what type of patients are candidates for the treatment. In this study, we investigated the anti-tumor efficacy of apatinib against 13 gastric cancer cell lines and found that it differed depending on the cell line. Using integrated wet and dry approaches, we showed that apatinib was a multi-kinase inhibitor of c-Kit, RAF1, VEGFR1, VEGFR2, and VEGFR3, predominantly inhibiting c-Kit. Notably, KATO-III, which was the most apatinib-sensitive among the gastric cancer cell lines investigated, was the only cell line expressing c-Kit, RAF1, VEGFR1, and VEGFR3 but not VEGFR2. Furthermore, we identified SNW1 as a molecule affected by apatinib that plays an important role in cell survival. Finally, we identified the molecular network related to SNW1 that was affected by treatment with apatinib. These results suggest that the mechanism of action of apatinib in KATO-III cells is independent of VEGFR2 and that the differential efficacy of apatinib was due to differences in expression patterns of receptor tyrosine kinases. Furthermore, our results suggest that the differential efficacy of apatinib in gastric cell lines may be attributed to SNW1 phosphorylation levels at a steady state. These findings contribute to a deeper understanding of the mechanism of action of apatinib in gastric cancer cells.
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Whether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (n = 216), we demonstrated that older adults (aged ≥65 years) had fewer vaccine-induced spike-specific CD4+ T cells including CXCR3+ circulating follicular helper T cells and the TH1 subset of helper T cells after the first dose, which correlated with their lower peak IgG levels and fewer systemic adverse effects after the second dose, compared with younger adults. Moreover, spike-specific TH1 cells in older adults expressed higher levels of programmed cell death protein 1, a negative regulator of T cell activation, which was associated with low spike-specific CD8+ T cell responses. Thus, an inefficient CD4+ T cell response after the first dose may reduce the production of helper T cytokines, even after the second dose, thereby lowering humoral and cellular immunity and reducing systemic reactogenicity. Therefore, enhancing CD4+ T cell response following the first dose is key to improving vaccine efficacy in older adults.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Anciano , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Vacunación/efectos adversos , Inmunidad Celular , Linfocitos T CD4-PositivosRESUMEN
Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.
RESUMEN
A combination of the detection of serum anti-Helicobacter pylori antibody and measurement of the level of serum pepsinogens (PG)s, known as the ABC method, has been used in screening for gastric cancer. The ABC method has been shown to be useful in urban and/or younger populations. The aim of this study was to assess whether this method is applicable for an agricultural population with a high incidence of gastric cancer. In all, 1048 healthy adults (401 men and 647 women) who participated in a mass survey in April 2005 were examined. Their serum samples were tested to determine the prevalence of anti-H. pylori antibody, and the levels of PG I and PG II were also measured to assess the presence of atrophic gastritis. Of the elderly subjects born before 1940, 59.4% were classified into groups C and D, with a high risk for gastric cancer, and only 22.7% were classified into group A, with the lowest risk. Of the middle-aged subjects born in the 1940s and the 1950s, 66.5% were classified into groups B-D. If the ABC method is performed in the mass screening for gastric cancer in this population, a large number of subjects will be identified for further examinations. The applicability of the ABC method should be evaluated before use in the screening for gastric cancer, particularly in an aging population with a high prevalence of H. pylori infection and atrophic gastritis.