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As a novel synthetic method for unsymmetrical macrocycles, we herein developed a post-synthetic modification of calix[4]arenes by insertion of a terminal alkyne into an inert C(methylene)-C(aryl) bond of the macrocyclic framework. In this transformation, C-iridated calix[4]arenes, readily synthesized through C-H bond activation of the parent calix[4]arene, undergoes C(methylene)-C(aryl) bond cleavage followed by insertion of an alkyne to provide a ring-expanded calix[4]arene complex. Removal of the iridium metal from the resulting complex was readily accomplished by a simple treatment with an acid. The developed sequential method affords novel unsymmetrical, monofunctionalized macrocyclic compounds via 3 steps from the parent calix[4]arene in good yield. The unique unsymmetrical structures of the alkyne-inserted macrocycles were evaluated by X-ray single crystal analyses. On the basis of theoretical calculations, we propose a reaction mechanism involving an uncommon C-C bond cleavage step through δ-carbon elimination for the ring enlargement process.
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BACKGROUND: Endoscopic submucosal dissection (ESD) is a potentially efficient therapeutic intervention for superficial esophageal cancer. Additional treatment such as chemoradiotherapy (CRT) or esophagectomy is recommended in cases of muscularis mucosa invasion with positive resection margins or lymphovascular invasion or submucosal layer invasion, which are considered noncurative ESD, due to an increased risk of lymph node metastasis. However, the adequacy of additional CRT after near-circumferential or full-circumferential noncurative ESD has not been fully discussed. In this study, we retrospectively evaluated the efficacy and toxicity of additional CRT for superficial esophageal squamous cell carcinoma (SCC) after near-circumferential or full-circumferential noncurative ESD, which was defined as a mucosal defect measuring ≥ 3/4 of the esophageal circumference. METHODS: We retrospectively evaluated 24 patients who received additional CRT for superficial esophageal SCC after near-circumferential or full-circumferential noncurative ESD between 2012 and 2018. Elective nodal irradiation (ENI) was performed in all patients and boost irradiation (BI) was performed after ENI in 4 patients with positive resection margins. The prescription doses of ENI and BI were 41.4 Gy in 23 fractions and 9 Gy in 5 fractions, respectively. Concurrent chemotherapy (a combination of cisplatin or nedaplatin and 5-fluorouracil) was administered to all patients. RESULTS: The 3-year and 5-year overall survival rates were 92% and 78%, respectively, while the 3-year and 5-year progression-free survival rates were 83% and 70%, respectively. Grade 2 esophageal stenosis occurred in 8 (33%) patients. There was no case of Grade 3 or worse esophageal stenosis. Among them, 4 (17%) patients developed stenosis before additional CRT, which persisted after the completion of additional CRT. The remaining 4 (17%) patients developed de novo stenosis within 5 months following the completion of additional CRT. One patient (4%) still requires regular bougie dilation. Grade 3 and Grade 4 acute toxicity, including anemia, neutropenia, thrombocytopenia, and esophagitis occurred in 1 (4%) and 0 (0%), 6 (25%) and 1 (4%), 1 (4%) and 0 (0%), and 1 (4%) and 0 (0%) patients, respectively. One (4%) patient who underwent salvage CRT for the out-of-field lymph node recurrence died with acute myeloid leukemia. CONCLUSIONS: Additional CRT is a viable treatment option even in patients who have undergone near-circumferential or full-circumferential noncurative ESD. Esophageal stenosis after additional CRT following near-circumferential or full-circumferential noncurative ESD is manageable and acceptable.
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Quimioradioterapia , Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Fluorouracilo , Humanos , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Masculino , Femenino , Quimioradioterapia/métodos , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Anciano , Persona de Mediana Edad , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Recent developments in mass spectrometry (MS) have revealed target antigens for membranous nephropathy (MN), including phospholipase A2 receptor and exostosin 1/exostosin 2 (EXT1/2). EXT1/2 are known antigens of autoimmune disease-related MN, especially membranous lupus nephritis. We describe the case of an elderly man who developed nephrotic syndrome followed by progressive renal dysfunction. CASE PRESENTATION: A 78-year-old man presented with rapidly progressive renal dysfunction with proteinuria and hematuria. Three years previously, he had developed leg edema but did not receive any treatment. Laboratory tests showed elevated anti-nuclear antibody (Ab), anti-dsDNA Ab titer, and hypocomplementemia, indicating systemic lupus erythematous. Myeloperoxidase anti-neutrophil cytoplasmic Ab (ANCA) and anti-glomerular basement membrane (GBM) Ab were also detected. The renal pathologic findings were compatible with crescentic glomerulonephritis (GN), whereas non-crescentic glomeruli exhibited MN without remarkable endocapillary or mesangial proliferative change. Immunofluorescence microscopy revealed glomerular IgG, C3, and C1q deposition. All IgG subclasses were positive in glomeruli. Anti-PLA2R Ab in serum was negative. MS analysis was performed to detect the antigens of MN, and EXT1/2 was detected in glomeruli. Therefore, we reached a diagnosis of membranous lupus nephritis concurrent with both ANCA-associated vasculitis and anti-GBM-GN. The simultaneous occurrence of these three diseases is extremely rare. CONCLUSIONS: This is the first report of EXT1/2-related membranous lupus nephritis concurrent with ANCA-associated vasculitis and anti-GBM-GN. This case demonstrates the usefulness of MS in diagnosing complicated cases of MN.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glomerulonefritis Membranoproliferativa , Glomerulonefritis Membranosa , Glomerulonefritis , Lupus Eritematoso Sistémico , Nefritis Lúpica , Anciano , Humanos , Masculino , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Anticuerpos Anticitoplasma de Neutrófilos , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/complicaciones , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/diagnóstico , Inmunoglobulina G , Lupus Eritematoso Sistémico/complicaciones , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnóstico , Espectrometría de Masas , N-AcetilglucosaminiltransferasasRESUMEN
BACKGROUND: Tetralogy of Fallot is the most common cyanotic congenital heart disease. Patients with the condition have a high risk of developing chronic kidney disease. Treatment of kidney disease in patients with complex hemodynamics presents unique challenges. However, there are very few reports on the treatment of end-stage renal failure in patients with tetralogy of Fallot. CASE PRESENTATION: We present a rare case of peritoneal dialysis in a 47-year-old man with tetralogy of Fallot who had not undergone intracardiac repair. Peritoneal dialysis successfully removed fluids and solutes without adversely affecting the patient's hemodynamics. Our patient was managed with peritoneal dialysis for 5 years before he succumbed to sepsis secondary to digestive tract perforation. CONCLUSIONS: In this paper, we discuss the importance of monitoring acid-base balance, changes in cyanosis, and hyperviscosity syndrome during peritoneal dialysis in patients with tetralogy of Fallot. Lower leg edema and B-type natriuretic peptide level were useful monitoring parameters in this case. This case illustrates that with attention to the patient's unique requirements, peritoneal dialysis can provide successful renal replacement therapy without compromising hemodynamics in patients with tetralogy of Fallot.
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Hemodinámica , Fallo Renal Crónico/terapia , Diálisis Peritoneal/métodos , Tetralogía de Fallot/fisiopatología , Procedimiento de Blalock-Taussing , Cianosis/fisiopatología , Edema , Cefalea/fisiopatología , Hemoglobinas/metabolismo , Humanos , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Terapia por Inhalación de Oxígeno , Flebotomía , Policitemia/sangre , Policitemia/etiología , Policitemia/terapia , Tetralogía de Fallot/sangre , Tetralogía de Fallot/complicaciones , Tetralogía de Fallot/terapiaRESUMEN
OBJECTIVE: To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy. METHODS: Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated. RESULTS: In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1-2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival. CONCLUSIONS: Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy.
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Metástasis Linfática/radioterapia , Cuello/patología , Neoplasias Primarias Desconocidas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/patología , Estudios RetrospectivosRESUMEN
PURPOSE: The aim of this study was to compare the outcomes of surgery and stereotactic body radiotherapy (SBRT) for elderly clinical stage I non-small cell lung cancer (NSCLC) patients. METHODS: Patients ≥80 years of age with clinical stage I NSCLC between August 2008 and December 2014 were treated either surgery or SBRT. Propensity score matching was performed to reduce bias in various clinicopathological factors. RESULTS: Surgery was performed in 57 cases and SBRT in 41 cases. In the surgery group, the operations included 34 lobectomies and 23 sublobar resections. In the SBRT group, 27 cases were given 48 Gy in 4 fractions, and 14 were given 60 Gy in 10 fractions. Similar characteristics were identified in age (82 years), gender (male:female ratio 2:1), tumor size (2.2 cm), carcinoembryonic antigen (3.6 ng/ml), Charlson comorbidity index (1), Glasgow prognostic scale (0), and forced expiratory volume in 1 s (1.7 L) after matching. Before matching, the 5-year overall survival (OS) in surgery (68.3%) was significantly better than that in SBRT (47.4%, p = 0.02), and the 5-year disease-specific survival (DSS) (94.1%, 78.2%, p = 0.17) was not significantly different between the groups. The difference in the 5-year OS became non-significant between the matched pairs (57.0%, 49.1%, p = 0.56). CONCLUSIONS: The outcomes of surgery and SBRT for elderly patients with the early stage NSCLC were roughly the same.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Neumonectomía , Puntaje de Propensión , Radiocirugia , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming α/ß = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS ≥ 2). BED was <20 Gy (in 27%), 20-30 Gy (24%), 30-40 Gy (36%) and ≥ 40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4-5 toxicity was reported. Pain relief was achieved in 52% at 2 months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1-9.9) at 6 months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2-76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.
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BACKGROUND/AIM: To investigate the clinical outcomes of concurrent chemoradiotherapy (CCRT) in patients with cervical esophageal carcinoma and analyze the prognostic factors. PATIENTS AND METHODS: Thirty-nine patients with cervical esophageal carcinoma were retrospectively identified among consecutive patients who received CCRT between November 2009 and September 2019 at our institution. The patients were treated by intensity-modulated radiation therapy (N=13) or three-dimensional conformal radiotherapy (N=26). RESULTS: The median follow-up period was 35 months (range=2-158 months). There were 32 men and 7 women with a median age of 66 years (range=50-83 years). Clinical stages were I in 6 patients, II in 4, III in 19, and IV in 10. Hypopharyngeal invasion was noted in 8 patients. The initial treatment responses were evaluated 3-6 weeks after the final session of CCRT: a complete response (CR) in 24 patients, a partial response (PR) in 13, and stable disease (SD) in 2. Two- and 5-year overall survival (OS) rates were 73.8 and 59.4%, respectively. Two- and 5-year progression-free survival (PFS) rates were 57.8 and 48.0%, respectively. A univariate analysis identified the initial treatment response (CR or non-CR) as a significant factor for OS (p=0.0002) and PFS (p=0.0026). The CR rate was 81.0% in patients with T1-3 and 33.3% in those with T4 (p=0.0038). CONCLUSION: Patients with cervical esophageal carcinoma in Nagasaki University Hospital in Japan achieved superior outcomes compared with previous studies. CR rate was higher in patients with T1-3 and correlated with better OS.
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Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies.
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BACKGROUND/AIM: This study was conducted to determine the prognosis and risk factors for survival in patients treated with stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This retrospective study analyzed 73 patients who underwent SBRT for HCC at Nagasaki University Hospital from December 2012 to July 2019 and examined the relationship between baseline information and prognosis. The Kaplan-Meier analysis and log-rank test were used to estimate the survival rate. Cox regression analysis was performed to determine the factors associated with overall survival (OS) after SBRT. RESULTS: The 1- and 2-year local control rates were 98.6% and 89.9%, respectively. Survival rates at 1, 3, and 5 years were 94.5%, 63.9%, and 45.5%, respectively. In the univariate analysis, baseline modified albumin-bilirubin grade (mALBI grade) [2b/3, hazard ratio (HR)=2.762, p=0.001], tumor size (≥2 cm, HR=2.479, p=0.003), and Barcelona Clinic Liver Cancer stage (BCLC) (B/C, HR=3.284, p<0.001) were significantly associated with poor prognosis. In multivariate analysis, baseline mALBI grade (2b/3, HR=2.283, p=0.009) and BCLC stage (B/C, HR=2.330, p=0.013) were significantly associated with poor prognosis. Only three patients (4.1%) developed grade 3 adverse events related to SBRT. CONCLUSION: SBRT is effective and safe in patients with HCC. The baseline mALBI grade is useful for predicting patient prognosis after SBRT. Patients with an mALBI grade of 1/2a are expected to have a better prognosis than patients with an mALBI grade of 2b/3.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirugia , Albúminas , Bilirrubina , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Pronóstico , Radiocirugia/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: Combination chemotherapy is used to treat advanced thymic carcinoma; however, the effects are insufficient. METHODS: Previously untreated patients with unresectable locally advanced thymic carcinoma received two cycles of 80 mg/m2 /day S-1 orally on days 1-14 plus 60 mg/m2 /day cisplatin intravenously on day 1, and concurrent radiotherapy (60 Gy). RESULTS: Three patients were enrolled into the study. Toxicity and survival were assessable in all patients, but the treatment response was only assessable in one patient. The study was terminated because of poor case recruitment. The patients' characteristics were as follows: male/female = 2/1; PS 0/1 = 2/1; median age (range) = 59 (55-72); and stage III/IV = 2/1. The patient in which the treatment response was assessed exhibited SD (response rate: 0%). In both nonevaluable cases, the second course of chemotherapy was judged to be post-protocol treatment because it was delayed by ≥14 days, but a CR and PR were achieved after the end of the study, respectively. G4 leukopenia/neutropenia and G3 febrile neutropenia occurred in one patient each (33%). The median time to tumor progression was 17.6 months, and the 1-, 2-, 3-, and 4-year survival rates were 67, 33, 33, and 33%, respectively. The median overall survival time was not reached, and the 1-, 2-, 3-, and 4-year survival rates were 100, 67, 67, and 67%, respectively. CONCLUSIONS: Although it was difficult to recruit patients, there was a long-term survivor >4 years who appeared to have achieved a CR, indicating that such chemoradiotherapy may be effective against locally advanced thymic carcinoma.
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Timoma , Neoplasias del Timo , Anciano , Quimioradioterapia/métodos , Cisplatino , Terapia Combinada , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia , Timoma/tratamiento farmacológico , Timoma/patología , Timoma/radioterapia , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/patología , Neoplasias del Timo/radioterapiaRESUMEN
We report a case of immunotactoid glomerulopathy (ITG) complicated with diffuse large B-cell lymphoma (DLBCL). A 68-year-old woman presented with leg edema and was diagnosed with nephrotic syndrome (NS). Renal biopsy revealed ITG. We treated the patient with prednisolone (20 mg/day) and she achieved complete remission of NS. Steroids were gradually reduced. After 1 year, the patient presented with a breast mass determined on biopsy to be DLBCL. She underwent six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Follow-up revealed complete remission of both DLBCL and ITG. NS recurred after 5 years and she was simultaneously diagnosed with recurrence of DLBCL in bone marrow. She underwent four cycles of R-EPOCH (rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin) therapy and entered remission for DLBCL. NS improved, but the treatment did not lead to remission. After 2 additional years, NS and DLBCL recurred again. She was administered rituximab and NS improved, although proteinuria tended to increase thereafter. One year later, we started prednisolone (10 mg/day), and proteinuria tended to decrease. She is currently undergoing outpatient follow-up. This case suggests that ITG with MGUS should be treated with the possibility of developing malignant hematological disease during the course.
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Glomerulonefritis , Linfoma de Células B Grandes Difuso , Síndrome Nefrótico , Anciano , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Glomerulonefritis/tratamiento farmacológico , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/tratamiento farmacológico , Prednisolona/uso terapéutico , Proteinuria/tratamiento farmacológico , Rituximab/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited-disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non-inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive-disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD-SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of AP in patients with LD-SCLC. METHODS: Treatment-naive patients with LD-SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/m2 /day (day 1) and AMR (day 1 to 3) will be administered with AHTRT (1.5 Gy/time, twice daily, 45 Gy in total). The initial AMR dose is set to 25 mg/m2 /day. RD and MTD will be determined by evaluating toxicities. DISCUSSION: Based on our previous study, the initial dose of AMR 25 mg/m2 is expected to be tolerated and acceptable. Here, we aim to determine whether treatment with AP and concurrent AHTRT would be an optimal choice with manageable toxicities for LD-SCLC.
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Quimioradioterapia , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Adulto , Anciano , Antraciclinas , Quimioradioterapia/efectos adversos , Cisplatino/uso terapéutico , Ensayos Clínicos Fase I como Asunto , Etopósido , Humanos , Neoplasias Pulmonares/terapia , Persona de Mediana Edad , Carcinoma Pulmonar de Células Pequeñas/terapia , Adulto JovenRESUMEN
OBJECTIVE: We compared outcomes after surgery or stereotactic body radiotherapy (SBRT) among patients with metachronous primary lung cancer (MPLC). METHODS: Patients with MPLC were treated with either surgery (2008-2018) or SBRT (2010-2018). We used propensity score matching (PSM) to reduce bias from various clinicopathological factors. MPLC was defined by the Martini and Melamed criteria. RESULTS: Of 77 patients, 51 underwent surgery and 26 received SBRT. Most median clinicopathological characteristics did not significantly differ between the surgery and SBRT groups (male sex: 67% vs 65%; age: 73 vs 77 years; time after first surgery: 6.2 vs 4.7 years; lobectomy as first procedure: 82% vs 85%; second tumor size: 11 vs 12 mm; clinical stage I: 96% vs 100%; CEA: 2.9 vs 3.0 ng/ml). However, the surgery group had significantly more ipsilateral second tumors (n = 71, 58%, P = 0.003), better performance status (P = 0.03), and preserved lung function (P = 0.02). Surgery, thus, tended to be selected for patients with good physical function and for the MPLC in the contralateral side. Five-year overall survival did not significantly differ between the surgery and SBRT groups, either before PSM (86.5% vs 65.8%, P = 0.24, log-rank) or after PSM (100% vs 84.4%, P = 0.73). CONCLUSIONS: Surgery and SBRT for MPLC patients are safe and feasible treatments with similar outcomes. However, this finding should be verified by a random controlled trial with a larger study cohort.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Neoplasias Primarias Secundarias/terapia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/secundario , Femenino , Humanos , Japón , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/secundario , Puntaje de Propensión , Radiocirugia , Análisis de SupervivenciaRESUMEN
Thymic carcinoma is a rare epithelial tumor of the thymus with a poor prognosis, and multimodal approaches are important for its treatment. Recently, a number of studies have indicated that S-1 treatment is effective against thymic carcinoma. S-1 plus cisplatin with concurrent radiotherapy is a commonly used treatment for other malignancies, including non-small cell lung cancer (NSCLC). In addition, its safety has been confirmed, and it has been reported to have a marked effect against thymic carcinoma. Therefore, we conducted a phase II study of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced thymic carcinoma, in which the overall response rate was employed as the primary endpoint. The secondary endpoints were overall survival, progression-free survival, and safety.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Timoma/terapia , Neoplasias del Timo/terapia , Adulto , Anciano , Cisplatino/administración & dosificación , Ensayos Clínicos Fase II como Asunto , Combinación de Medicamentos , Humanos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ácido Oxónico/administración & dosificación , Pronóstico , Proyectos de Investigación , Tegafur/administración & dosificación , Timoma/patología , Neoplasias del Timo/patología , Adulto JovenRESUMEN
OBJECTIVES: Because chemoradiotherapy using cisplatin and S-1, an oral fluoropyrimidine, is effective for unresectable non-small cell lung cancer (NSCLC), an induction setting was used in a multicenter phase II study (Clinical trial number: UMIN000008205). The correlations of relapse and clinicopathological factors were analyzed. METHODS: We defined locally advanced NSCLC as pathologically proven chest wall invasion or hilar and/or mediastinal lymph node metastases by endobronchial ultrasound-guided transbronchial needle aspiration. The patients received two courses of S-1 administration for 14 days and intravenous cisplatin injection on day 8. A total dose of 40 Gy radiotherapy was concurrently received. Surgical resection was performed after completion of the treatment. RESULTS: Of the 23 eligible patients, 18 had stage IIIA and 5 had stage IIB NSCLC. Twenty of the eligible patients (87.0%) completed the regimen. Six (26.1%) complete responses were identified and 12 cases (52.2%) were histopathologically downstaged by induction chemoradiotherapy (ICRT). The 3-year overall survival rate was 58.1% and relapse-free survival (RFS) rate was 52.0%, respectively. Among several clinicopathological parameters, univariate RFS analysis identified that only downstaging was significantly associated with longer RFS times (p = 0.003). The radiological response did not reflect pathological response. When the variables of preoperative pathologically proven N2 metastasis, pathological ICRT effectiveness, and downstaging were included in the Cox proportional hazard modes, only the parameter of downstaging displayed significant hazard ratio (hazard ratio 0.13, p = 0.010). CONCLUSION: This protocol is considered an option among preoperative therapies and has obvious benefits for pathologically downstaged cases. CLINICAL TRIAL NUMBER: UMIN000008205. TRIAL REGISTRATION DATE: June 19, 2012.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/métodos , Neoplasias Pulmonares/terapia , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Ácido Oxónico/uso terapéutico , Tasa de Supervivencia , Tegafur/uso terapéuticoRESUMEN
BACKGROUND: Amrubicin and cisplatin is one of the active regimens used to treat patients with extensive-disease (ED)-small cell lung cancer (SCLC), whereas combined therapy involving chemotherapy and concurrent thoracic radiotherapy is the standard treatment for limited-disease (LD)-SCLC. PURPOSE: This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of amrubicin and cisplatin with concurrent thoracic radiotherapy (TRT) for LD-SCLC. PATIENTS AND METHODS: Patients that fulfilled the following eligibility criteria were enrolled: being aged ≤ 75 years and chemotherapy-naïve and having a performance status (PS) of 0-1, LD-SCLC, and adequate organ function. The patients received escalating doses of amrubicin on days 1, 2, and 3, and a fixed 60-mg/m2 dose of cisplatin on day 1. Four cycles of chemotherapy were administered, with each cycle lasting 4 weeks. TRT involving 2 Gy/day, once daily, commenced on day 2 of the first cycle of chemotherapy. The initial dose of amrubicin was 20 mg/m2 (level 1), and the dose was escalated to 25 mg/m2 (level 2) and then 30 mg/m2 (level 3). RESULTS: Eight patients from three institutions were enrolled at three dose levels. The patients' characteristics were as follows: male/female: 3/5; median age (range): 68.5 (60-73); PS 0/1: 4/4; stage IIIA/IIIB disease: 3/5. Both level 3 patients experienced DLT (grade 4 neutropenia and/or leukopenia lasting > 4 days). Level 3 was defined as the MTD, and level 2 was recommended as the dose for this regimen. Seven patients exhibited partial responses, and 1 displayed progressive disease (response rate: 88%). The median progression-free survival and overall survival periods were 11.1 and 39.5 months, respectively. No treatment-related deaths occurred. CONCLUSIONS: When this regimen was combined with TRT for LD-SCLC, the MTD was 30 mg/m2 for amrubicin and 60 mg/m2 for cisplatin. In addition, neutropenia and leukopenia were DLT, and doses of 25 mg/m2 for amrubicin and 60 mg/m2 for cisplatin are recommended for this regimen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Anciano , Antraciclinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Supervivencia sin Progresión , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Tasa de SupervivenciaRESUMEN
Urachal carcinoma is an extremely rare malignant tumor arising from the urachus in the fetus. We report a patient who developed urachal carcinoma 18 years after kidney transplantation. A 59-year-old man was admitted because of abdominal pain and massive ascites. He had undergone kidney transplantation 18 years earlier and had end-stage renal disease requiring dialysis. Abdominal CT showed massive ascites and an abdominal wall cystic mass separated from the peritoneal cavity. Hemodialysis was started, and paralytic ileus was diagnosed and treated. His ileus symptoms improved temporarily, but he died of myocardial infarction. An autopsy was performed, which revealed cystadenocarcinoma in the abdominal wall mass, leading to a diagnosis of urachal carcinoma.
RESUMEN
AIM: To assess the efficacy and feasibility of alternating chemoradiotherapy for esophageal cancer. MATERIALS AND METHODS: Patients, with previously untreated esophageal cancer, Eastern Cooperative Oncology Group performance status of 0 to 2, age 20 to 75 years and sufficient organ function, were eligible for this study. Three cycles of systemic chemotherapy with the continuous infusion of 3500 mg/m2 of 5-fluorouracil (5-FU: days 1-5) and a 6-h infusion of nedaplatin (NDP; day 6: 120-140 mg/m2), were accompanied by thoracic irradiation of 63 Gy in 35 fractions over 7 weeks. Radiation therapy was stopped during systemic chemotherapy (alternating setting). In the phase I part, the dose of nedaplatin was increased to define dose-limiting toxicities. For the phase II part, patients with distant metastasis were excluded. RESULTS: From 1998 through 2002, 40 patients were recruited for this protocol study. The median patient age was 54 years (range, 49-65 years) for the phase I and 58 years (range, 44-73 years) for the phase II trials. There were 35 men and 5 women in this study. For the phase I part (n = 15), the maximal tolerated dose of NDP was 140 mg/m2; thus, the recommended dose was 130 mg/m2. Twenty-five patients were treated with the recommended doses in the phase II part of the study. Ten patients had T4 disease and 14 patients had stage IV disease in the phase II part of the study. The overall survival rates at 1 and 2 years were 58.9% and 45.9%, respectively. The most frequent toxicities were leukopenia (grade 3 or greater: 80%), followed by thrombocytopenia (56%), granulocytopenia (56%) and anemia (28%). Radiation esophagitis of grade 3 or greater developed in 6 patients (24%). Two patients died of radiation pneumonitis. The actual dose intensities of NDP and 5-FU were 68.8% and 73.3%, respectively. CONCLUSION: This intensive treatment for esophageal cancer was feasible and effective; however, moderate-to-severe toxicity occurred. This protocol warrants further clinical evaluation in a multi-institutional prospective study.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Esquema de Medicación , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversosRESUMEN
OBJECTIVES: This study seeks to further characterize the role of exercise testing in the elderly for prognosis and diagnosis of coronary artery disease. BACKGROUND: Recent exercise testing guidelines have recognized that statements regarding the elderly do not have an adequate evidence-based quality because the studies they are based on have limitations in sample size and design. The Duke Treadmill Score has been recommended for risk stratification, but recent evidence has suggested that it does not function in the elderly. METHODS: The study population consisted of male veterans (1872 patients >or=65 years; 3798 patients <65 years) who underwent routine clinical exercise testing with a mean follow-up of six years. A subset who underwent coronary angiography as clinically indicated (elderly, n = 405; younger, n= 809) were included. The primary outcome for all subjects was cardiovascular mortality with coronary angiographic findings as the outcome in those selected for angiography. RESULTS: In survival analysis, exercise-induced ST depression was prognostic in both age groups only when cardiovascular death was considered as the end point. Peak metabolic equivalents were the most significant predictor for both age groups only when all-cause death was considered as the end point. New age-specific prognostic scores were developed and found to be predictive for cardiovascular mortality in the elderly. Moreover, in the angiographic subset of the elderly, a specific diagnostic score provided significantly better discrimination than exercise ST measurements alone. For any new score, there is a need for validation in another elderly population. CONCLUSIONS: The mortality end point affected the choice of prognostic variables. This study demonstrates that exercise test scores can be helpful for the diagnosis and prognosis of coronary disease in the elderly.