RESUMO
PURPOSE: Clinical trials have demonstrated higher complete response rates in the immuno-oncology-based combination arms than in the tyrosine kinase inhibitor arms in patients with metastatic renal cell carcinoma. We aimed to characterize real-world patients who experienced complete response to the contemporary first-line therapies. MATERIALS AND METHODS: Using the International Metastatic Renal Cell Carcinoma Database Consortium, response-evaluable patients who received frontline immuno-oncology-based combination therapy or tyrosine kinase inhibitor monotherapy were analyzed. Baseline characteristics of patients and post-landmark overall survival were compared based on best overall response, as per RECIST 1.1. RESULTS: A total of 52 (4.6%) of 1,126 and 223 (3.0%) of 7,557 patients experienced complete response to immuno-oncology-based and tyrosine kinase inhibitor therapies, respectively (P = .005). An adjusted odds ratio for complete response achieved by immuno-oncology-based combination therapy (vs tyrosine kinase inhibitor monotherapy) was 1.56 (95% CI 1.11-2.17; P = .009). Among patients who experienced complete response, the immuno-oncology-based cohort had a higher proportion of non-clear cell histology (15.9% and 4.7%; P = .016), sarcomatoid dedifferentiation (29.8% and 13.5%; P = .014), and multiple sites of metastases (80.4% and 50.0%; P < .001) than the tyrosine kinase inhibitor cohort. Complete response was independently associated with post-landmark overall survival benefit in both the immuno-oncology-based and tyrosine kinase inhibitor cohorts, giving respective adjusted hazard ratios of 0.17 (95% CI 0.04-0.72; P = .016) and 0.28 (95% CI 0.21-0.38; P < .001). CONCLUSIONS: The complete response rate was not as high in the real-world population as in the clinical trial population. Among those who experienced complete response, several adverse clinicopathological features were more frequently observed in the immuno-oncology-based cohort than in the tyrosine kinase inhibitor cohort. Complete response was an indicator of favorable overall survival.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Resultado do Tratamento , Modelos de Riscos Proporcionais , Imunoterapia , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: The Geriatric Nutritional Risk Index (GNRI) has been reported as a screening tool to assess the nutrition-related risk with mortality in older patients and those with the various diseases. However, the prognostic value of GNRI in metastatic renal cell carcinoma (mRCC) patients receiving nivolumab therapy remains unclear. METHODS: Fifty-six consecutive patients with mRCC receiving nivolumab between September 2013 and August 2020 at our institution were retrospectively analyzed. The survival outcomes and prognostic factors associated with overall survival (OS) were statistically analyzed. RESULTS: Thirteen and forty-three patients were classified with low (GNRI < 92) and high (GNRI ≥ 92) GNRI, respectively. Patients with low GNRI demonstrated significantly shorter OS (P = 0.0002) than those with high GNRI. In multivariate analysis, GNRI at the time of nivolumab (P = 0.008) was extracted as the predictor for OS in addition to Karnofsky performance status (KPS) (P = 0.016). Integration of the GNRI into the International Metastatic Renal Cell Cancer Database Consortium (IMDC) risk classification improved the c-index from 0.761 to 0.833 (combination of GNRI with IMDC risk classification) and to 0.778 (substitution of GNRI with KPS in IMDC risk classification). CONCLUSIONS: GNRI was a significant prognostic biomarker in mRCC patients receiving nivolumab.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Idoso , Carcinoma de Células Renais/patologia , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Neoplasias Renais/patologia , Prognóstico , Estado Nutricional , Avaliação NutricionalRESUMO
BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. METHODS: This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. DISCUSSION: This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358.
Assuntos
Distinções e Prêmios , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/radioterapia , Micrometástase de Neoplasia , Imagem de Difusão por Ressonância MagnéticaRESUMO
BACKGROUND: Prostate cancer localization is reportedly associated with the laterality of lymph node metastasis. Thus, it may be feasible to predict side-specific lymph node metastasis (LNM) at radical prostatectomy (RP). To investigate whether multiparametric magnetic resonance imaging and biopsy findings can predict side-specific negative LNM and to explore the feasibility of unilateral lymph node dissection (LND) at RP. METHODS: A total of 500 patients who were diagnosed with prostate cancer with prebiopsy multiparametric magnetic resonance imaging of the prostate and subsequent prostate biopsy and who underwent RP and extended LND without neoadjuvant treatment were enrolled. Multiparametric magnetic resonance imaging, biopsy findings, and LNM were assessed for each side. The negative predictive value (NPV) of multiparametric magnetic resonance imaging or biopsy or both for ipsilateral LNM was examined. RESULTS: LNM was found in 9.2% (46/500) and 15.6% (28/180) of patients in the overall and high-risk cohorts, respectively. Magnetic resonance imaging and biopsy findings were negative in 408 and 262 sides, respectively, in the overall cohort and 144 and 100 sides, respectively, in the high-risk cohort. The NPVs of magnetic resonance imaging, biopsy, and both for ipsilateral LNM were 98.3%, 98.5%, and 99.1%, respectively, in the overall cohort, and 95.8%, 97.1%, and 97.6%, respectively, in the high-risk cohort. CONCLUSIONS: Unilateral LND may be indicated based on side-specific LNM risk as assessed by prebiopsy multiparametric magnetic resonance imaging and biopsy.
Assuntos
Próstata , Neoplasias da Próstata , Biópsia , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Imageamento por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: There are few reports from Japan about the outcomes of intensity-modulated radiation therapy for localized prostate cancer. This study was aimed at assessing the efficacy and toxicity of intensity-modulated radiation therapy in patients with intermediate- or high-risk prostate cancer. METHODS: We conducted a review of the data, retrieved from our institutional database, of patients who had received intensity-modulated radiation therapy for localized prostate cancer at a radiation dose of 78 Gy in 39 fractions. Data of 201 patients with intermediate-risk prostate cancer and 311 patients with high-risk prostate cancer were analyzed. RESULTS: The median follow-up period after the completion of intensity-modulated radiation therapy was 100 months (range, 24-154). The rates of cause-specific survival, overall survival, metastasis-free survival and biochemical recurrence-free survival in the intermediate-risk patients were 99, 95, 95 and 94% at 5 years and 99, 91, 90 and 86% at 8 years, respectively; the corresponding rates in the high-risk patients were 100, 97, 91 and 84% at 5 years and 96, 92, 84 and 76% at 8 years, respectively. The crude incidence of late grade 2-3 genitourinary toxicity was 28.1%, and that of late grade 3 genitourinary toxicity was 2.0%. The crude incidence of late grade 2 gastrointestinal toxicity was 5.1%, and there were no cases of late grade 3 gastrointestinal toxicity. CONCLUSIONS: Our data demonstrated that intensity-modulated radiation therapy is effective for patients with localized intermediate-risk or high-risk prostate cancer while having minimal toxicity.
Assuntos
Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Humanos , Masculino , Incidência , Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Resultado do Tratamento , Sistema UrogenitalRESUMO
OBJECTIVES: To investigate the tumor shrinkage patterns of patients with metastatic renal cell carcinoma treated with nivolumab monotherapy. METHODS: Forty-four consecutive patients with metastatic renal cell carcinoma treated with nivolumab monotherapy (81 metastatic and four primary lesions) between September 2013 and December 2020 were retrospectively analyzed. The tumor shrinkage rate of individual visceral and lymph node metastatic lesions and the primary site lesions treated with nivolumab monotherapy, as well as the association between overall survival and pretreatment tumor size, were statistically assessed. RESULTS: Pretreatment tumor size for the total and individual target lesions, which included kidneys, lungs, pancreas, and lymph nodes, were not correlated with tumor shrinkage rate. The tumor shrinkage rate was found to have no significant association with pretreatment tumor size between any organ. In addition, there is no significant difference in tumor shrinkage rate between larger (>median value) and smaller (Assuntos
Carcinoma de Células Renais
, Neoplasias Renais
, Carcinoma de Células Renais/diagnóstico por imagem
, Carcinoma de Células Renais/tratamento farmacológico
, Humanos
, Neoplasias Renais/diagnóstico por imagem
, Neoplasias Renais/tratamento farmacológico
, Nivolumabe/uso terapêutico
, Estudos Retrospectivos
RESUMO
OBJECTIVE: To assess the prognostic and predictive ability of early C-reactive protein (CRP) kinetics, dynamic changes in CRP levels, in patients with advanced urothelial cancer treated with pembrolizumab. PATIENTS AND METHODS: We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line or later settings. Patients were divided into three early CRP kinetics groups: non-elevated (baseline CRP < 5 mg/L), responder (baseline CRP ≥ 5 mg/L and CRP decreased below baseline at least once within 30 days), and non-responder (baseline CRP ≥ 5 mg/L and CRP never decreased to baseline within 30 days). Association between early CRP kinetics and pembrolizumab efficacy including objective response rate (ORR), disease control rate (DCR), and overall survival (OS) were evaluated. RESULTS: Based on early CRP kinetics, 40, 27, and 30 patients were classified as non-elevated, responder, and non-responder, respectively. ORR and DCR were 33% and 60% in non-elevated, 30% and 48% in responder, and 17% and 40% in non-responder; without a statistically significant difference. OS was significantly different among the non-elevated, responder, and non-responder groups (p < 0.01), with 1-year survival rates of 69%, 61%, and 31%, respectively. Early CRP kinetics could discriminate the OS of patients without objective response. Non-responder was an independent predictor for OS (HR 3.65, p < 0.01), as well as liver metastasis and ECOG PS ≥ 2. CONCLUSION: Early CRP kinetics is associated with survival of advanced urothelial cancer patients treated with pembrolizumab and could be a potential biomarker for clinical benefit from immune checkpoint inhibitors.
Assuntos
Biomarcadores , Proteína C-Reativa/metabolismo , Neoplasias Urológicas/sangue , Neoplasias Urológicas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Prognóstico , Resultado do Tratamento , Neoplasias Urológicas/tratamento farmacológicoRESUMO
BACKGROUND: We aimed to establish an external validation of the Briganti 2019 nomogram in a Japanese cohort to preoperatively evaluate the probability of lymph node invasion in patients with high-risk, clinically localized prostate cancer. METHODS: The cohort consisted of 278 patients with prostate cancer diagnosed using magnetic resonance imaging-targeted biopsy who underwent radical prostatectomy and extended pelvic lymph node dissection from 2012 to 2020. Patients were rated using the Briganti 2019 nomogram, which evaluates the probability of lymph node invasion. We used the area under curve of the receiver operating characteristic analysis to quantify the accuracy of the nomogram. RESULTS: Nineteen (6.8%) patients had lymph node invasion. The median number of lymph nodes removed was 18. The area under the curve for the Briganti 2019 was 0.71. When the cutoff was set at 7%, 84 (30.2%) patients with extended pelvic lymph node dissection could be omitted, and only 1 (1.2%) patient with lymph node invasion would be missed. Sensitivity, specificity, and negative predictive values at the 7% cutoff were 94.7, 32.0, and 98.8%, respectively. CONCLUSION: This external validation showed that the Briganti 2019 nomogram was accurate, although there may still be scope for individual adjustments.
RESUMO
Cytotoxic chemotherapy, including cyclophosphamide, vincristine, and dacarbazine (CVD) therapy, is widely used to treat metastatic pheochromocytoma and paraganglioma. Because these diseases are rare, studies are needed to establish treatment strategies. This was a single-center and retrospective study to analyze the efficacy of chemotherapy for patients with metastatic pheochromocytoma and paraganglioma diagnosed in 1983-2020. Clinical characteristics, tumor volume response, biochemical response based on catecholamine level, overall survival, and progression-free survival were evaluated. Patients with a complete response or partial response in tumor volume or catecholamine level were classified as responders. Sixteen patients were administered chemotherapy for a median of 16.5 cycles (interquartile range, 10-42). The tumor volume response was classified as follows: partial response (N = 4), stable disease (N = 9), and progressive disease (N = 3) (disease control rate = 81%). The biochemical responses were as follows: complete response (N = 2), partial response (N = 5), no change (N = 3), and progressive disease (N = 1) (disease control rate = 91%). The 5-year survival rate was 50% (95% confidence interval [CI], 21-74%) and median overall survival was 4.4 years (95% CI, 2.4 years-not reached). Overall survival and progression-free survival between responders and nonresponders were not statistically different. One patient developed myelodysplastic syndrome during CVD therapy. In conclusion, chemotherapy achieved disease control among more than half of patients, although survival did not differ between responders and nonresponders. Further fundamental research and prospective trials are needed to analyze the efficacy of CVD therapy.
Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Antineoplásicos/uso terapêutico , Paraganglioma/tratamento farmacológico , Feocromocitoma/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraganglioma/secundário , Paraganglioma/cirurgia , Feocromocitoma/secundário , Feocromocitoma/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. While mitotane is the only agent approved for ACC, clinical data are scarce, especially in the Asian population. We reviewed 10 patients with ACC who received mitotane as a single agent or in combination with other agents in our institution. Patient characteristics, clinical outcomes, and toxicities were analyzed. Mitotane was administered to 2 patients as an adjuvant therapy and to 8 patients for systemic control. In the latter 8 patients, 1 patient had locally advanced disease and 1 had metastatic disease at the time of initial diagnosis, whereas the other 6 patients experienced metastatic relapse at mitotane initiation. The administered regimen was mitotane alone in 7 patients, and mitotane plus cytotoxic chemotherapy in 3 patients. The initial daily mitotane dose was 3.0 g in 2 patients, 1.5 g in 7 patients, and 1.0 g in 1 patient. The median duration of treatment was 3.7 (range, 0.7-22.1) months. In 8 systemic cases, the median overall survival from chemotherapy initiation was 7.2 months, and only 1 patient survived over 1 year. The median interval from mitotane termination to death in systemic cases was 2.8 months, and the cause was progressive disease in 4 patients and toxicity (hallucination, mycobacteriosis, or liver injury) in 3 patients. As a second-line regimen, 2 systemic cases and 1 adjuvant case were enrolled in clinical trials. Our analysis exhibited extremely poor prognosis under mitotane-based regimens, and further treatment strategies are warranted to improve outcomes.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/patologia , Antineoplásicos Hormonais/uso terapêutico , Humanos , Japão , Mitotano/efeitos adversos , Recidiva Local de NeoplasiaRESUMO
OBJECTIVES: To evaluate the efficacy and safety profiles of first-line etoposide, ifosfamide and cisplatin and primary prophylaxis with pegfilgrastim as first-line chemotherapy for disseminated germ cell cancer. METHODS: This study reviewed 154 consecutive patients with previously untreated disseminated germ cell cancer who received first-line etoposide, ifosfamide and cisplatin between 1995 and 2020. Of these, 54 patients were managed with primary prophylaxis using pegfilgrastim (primary prophylaxis group), and 100 were managed with the therapeutic use of short-acting granulocyte colony-stimulating factor (non-primary prophylaxis group). RESULTS: The International Germ Cell Cancer Collaborative Group classification identified 90 (58%)/40 (26%)/24 (16%) patients with good/intermediate/poor prognosis, respectively. Overall, 139 patients (90%) were disease free after etoposide, ifosfamide and cisplatin with/without post-chemotherapy surgery. The median relative dose intensity of etoposide, ifosfamide and cisplatin was 96%, and there was a significant difference between the primary prophylaxis and non-primary prophylaxis groups (100% vs 90%, P < 0.01). The 5-year salvage treatment-free and overall survival rates were 83% and 94%, respectively. In total, 138 patients (90%) developed grade 4 hematological toxicities, and there were no treatment-related deaths due to myelosuppression. Grade 4 neutropenia was less commonly observed in the primary prophylaxis group compared with the non-primary prophylaxis group (80% vs 95%, P < 0.01). CONCLUSIONS: This is the largest study of first-line etoposide, ifosfamide and cisplatin, and its sufficient efficacy and safety profiles are confirmed in current clinical practice. Primary prophylaxis using pegfilgrastim might further improve the feasibility of etoposide, ifosfamide and cisplatin.
Assuntos
Ifosfamida , Neoplasias Embrionárias de Células Germinativas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Etoposídeo/efeitos adversos , Estudos de Viabilidade , Humanos , Ifosfamida/efeitos adversos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológicoRESUMO
OBJECTIVE: To report our institutional experience with treatment of primary genitourinary soft tissue sarcoma. METHODS: We retrospectively reviewed the medical records of adult soft tissue sarcoma patients treated between March 2005 and May 2019. The primary tumor sites included the prostate, kidney, urinary bladder and the paratesticular structures. RESULTS: A total of 19 patients - 16 men (84%) and three women (16%) - were enrolled in the study. The median age was 41 years (range 20-79 years). The most common primary site was the prostate (in eight patients; 42%), and prostatic sarcoma patients were younger than patients with sarcomas of other origins. The most common histological subtype was leiomyosarcoma (in five patients; 26%). The overall survival rates after 1, 3 and 5 years were 61.5%, 34.4% and 25.8%, respectively. The median survival time was 20.7 months (95% confidence interval 5.9-35.5 months). Univariate analysis showed that an absence of metastasis at diagnosis and complete surgical resection were predictive of favorable survival. In the chemotherapy group, the objective response rate was 20.5%. Pazopanib was administered to nine patients in the late-line setting, and the objective response rate was 11.1%; six grade ≥3 adverse events were observed in three patients. CONCLUSIONS: Inoperable metastatic genitourinary soft tissue sarcoma remains difficult to treat, as previously reported. Further investigation on this malignancy, including optimization of currently available antitumor drugs and the development of novel therapeutic agents, is required.
Assuntos
Antineoplásicos , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE: The controlling nutritional status (CONUT) score, consisting of albumin, lymphocytes and total cholesterol, is a validated, objective tool for nutritional assessment. Patients with advanced cancer frequently have malnutrition in association with cachexia and chronic inflammation. We explored the prognostic significance of the CONUT score in patients with advanced renal cell carcinoma receiving nivolumab. MATERIALS AND METHODS: This retrospective study included 60 patients with stage IV renal cell carcinoma treated with nivolumab after failure of prior tyrosine kinase inhibitors at 2 cancer centers between 2016 and 2019. Associations of the CONUT score with progression-free survival, cancer specific survival and tumor shrinkage rate were assessed. RESULTS: The median (range) CONUT score was 2 (0-10). During followup periods 29 and 14 patients exhibited disease progression and died of cancer, respectively. Both progression-free survival and cancer specific survival were significantly stratified by CONUT scores of 0 to 1, 2 to 4 and 5 or more (p=0.002). A CONUT score of 5 or more (versus score 0 to 1) was independently associated with unfavorable progression-free survival (HR 5.18, p=0.003) and cancer specific survival (HR 15.34, p=0.014), as was the absence of prior nephrectomy (HR 4.23, p=0.004 and HR 6.57, p=0.001, respectively). C-indices of the CONUT score for predicting progression-free survival and cancer specific survival were 0.694 and 0.737, respectively. The CONUT score was significantly associated with the best response to nivolumab with the median tumor shrinkage rate of -23%, +8% and +24% for CONUT scores of 0 to 1, 2 to 4 and 5 or more, respectively (p=0.021). CONCLUSIONS: The CONUT score may be useful to predict the clinical outcomes and therapeutic response in patients with advanced renal cell carcinoma receiving nivolumab.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Caquexia/diagnóstico , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Nivolumabe/uso terapêutico , Avaliação Nutricional , Idoso , Antineoplásicos Imunológicos/farmacologia , Caquexia/sangue , Caquexia/etiologia , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Quimioterapia Adjuvante/métodos , Colesterol/sangue , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Nefrectomia , Nivolumabe/farmacologia , Estado Nutricional/fisiologia , Prognóstico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Albumina Sérica Humana/análiseRESUMO
BACKGROUND: Nivolumab, which has a promising anti-tumor efficacy and a manageable safety profile, has being rapidly introduced in metastatic renal cell cancer therapy in Japan. We evaluated the efficacy and adverse events of nivolumab in real world clinical practice in Japan. METHODS: The medical records of 45 consecutive patients who started treatment with nivolumab, up to September 2018, were reviewed and statistically analyzed. RESULTS: The median follow-up period was 22.3 months. The best responses were a complete response in three patients (8%), a partial response in 14 patients (36%), stable disease in 14 patients (36%), and progressive disease in eight patients (20%). The median progression-free survival period and 1 year progression-free survival rate were 14.9 months and 54.5%, respectively. The estimated overall survival period and 1-year and 2-year overall survival rates from initiation of nivolumab were not reached, and 91.1%, and 86.2%, respectively. Twenty-seven patients (60%) experienced adverse events including four (10%) severe adverse events (Grade 3 or 4). The most common adverse event was rash (n = 9, 20%). Five patients discontinued nivolumab therapy, because of an adverse event (Grade 3 diarrhea, one patient; Grade 2 fatigue, one patient; Grade 3 uveitis, two patients; and Grade 3 adrenal insufficiency, one patient). CONCLUSIONS: Nivolumab has a relatively favorable efficacy and safety profile for Japanese metastatic renal cell cancer patients in clinical practice.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma de Células Renais/patologia , Diarreia/induzido quimicamente , Exantema/induzido quimicamente , Humanos , Japão , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Accurate prediction of the prognosis of RCC using a single biomarker is challenging due to the genetic heterogeneity of the disease. However, it is essential to develop an accurate system to allow better patient selection for optimal treatment strategies. ARL4C, ECT2, SOD2, and STEAP3 are novel molecular biomarkers identified in earlier studies as survival-related genes by comprehensive analyses of 43 primary RCC tissues and RCC cell lines. METHODS: To develop a prognostic model based on these multiple biomarkers, the expression of four biomarkers ARL4C, ECT2, SOD2, and STEAP3 in primary RCC tissue were semi-quantitatively investigated by immunohistochemical analysis in an independent cohort of 97 patients who underwent nephrectomy, and the clinical significance of these biomarkers were analyzed by survival analysis using Kaplan-Meier curves. The prognostic model was constructed by calculation of the contribution score to prognosis of each biomarker on Cox regression analysis, and its prognostic performance was validated. RESULTS: Patients whose tumors had high expression of the individual biomarkers had shorter cancer-specific survival (CSS) from the time of primary nephrectomy. The prognostic model based on four biomarkers segregated the patients into a high- and low-risk scored group according to defined cut-off value. This approach was more robust in predicting CSS compared to each single biomarker alone in the total of 97 patients with RCC. Especially in the 36 metastatic RCC patients, our prognostic model could more accurately predict early events within 2 years of diagnosis of metastasis. In addition, high risk-scored patients with particular strong SOD2 expression had a much worse prognosis in 25 patients with metastatic RCC who were treated with molecular targeting agents. CONCLUSIONS: Our findings indicate that a prognostic model based on four novel biomarkers provides valuable data for prediction of clinical prognosis and useful information for considering the follow-up conditions and therapeutic strategies for patients with primary and metastatic RCC.
Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , Fatores de Ribosilação do ADP , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Proteínas de Ciclo Celular , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Nefrectomia , Oxirredutases , Prognóstico , Proteínas Proto-Oncogênicas , Medição de Risco , Superóxido DismutaseRESUMO
OBJECTIVES: To analyze the incidence and predictors of deep vein thrombosis (DVT) in patients with elevated D-dimer prior to surgery for urologic malignancy. METHODS: Between January 2015 and September 2017, 987 consecutive patients underwent surgery for urologic malignancy under general anesthesia in our institution. Of these, 191 patients underwent preoperative venous ultrasonography of the lower extremities for DVT due to elevated D-dimer. We analyzed the incidence and predictors of DVT in these patients. RESULTS: The median age was 69 years. DVT was detected in 18% of patients (35/191). Multivariate analysis showed that the primary site of urologic malignancy (p < 0.01) and older age (p < 0.01) were independent predictors of DVT. Patients with bladder cancer had the highest incidence of DVT. When bladder cancer and age of 70 or older were defined as predictors for DVT, the incidence of DVT in zero, 1, and 2 predictors was 3.4% (3/89), 29% (22/77), and 44% (11/25), respectively. CONCLUSIONS: DVT was found in 18% of patients with elevated D-dimer prior to surgery for urologic malignancy. Bladder cancer patients and older patients in whom D-dimer has been elevated should undergo careful early examination for DVT.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/cirurgia , Trombose Venosa/complicações , Trombose Venosa/epidemiologia , Idoso , Feminino , Humanos , Incidência , Perna (Membro)/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias , Análise de Regressão , Fatores de Risco , Ultrassonografia , Neoplasias Urológicas/sangue , Veias/diagnóstico por imagem , Trombose Venosa/sangueRESUMO
INTRODUCTION: In spite of the high incidence of infectious complications (ICs), appropriate duration of antimicrobial prophylaxis (AMP) for radical cystectomy (RC) with intestinal urinary diversion (IUD) has not been established. We compared the incidence of ICs after RC with IUD in patients using only intraoperative AMP or extended duration AMP. Risk factors for ICs were also investigated. PATIENTS AND METHODS: One hundred twenty-three consecutive patients who underwent RC with IUD were divided into 2 groups based on the AMP duration (intraoperative only vs. extended duration for a median of 3 days). Between the groups, the incidence of ICs was compared. Risk factors for ICs were investigated in multivariate analysis. RESULTS: The IC rate was 44%. No significant difference was found in the rate of ICs between the groups. The IC rate was significantly higher in patients with lower estimated glomerular filtration rate (eGFR). Rates of ICs were 60 and 38% in patients with eGFR of less than 60 and equal or more than 60 mL/min/1.73 m2, respectively. CONCLUSIONS: Our result indicates that AMP that is administered more than intraoperatively may be excessive in RC with IUD. Patients with a lower eGFR should be particularly cared for postoperative ICs.
Assuntos
Antibioticoprofilaxia , Cistectomia , Cuidados Intraoperatórios , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/prevenção & controle , Derivação Urinária , Infecções Urinárias/prevenção & controle , Idoso , Antibioticoprofilaxia/métodos , Cistectomia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Tempo , Derivação Urinária/efeitos adversos , Infecções Urinárias/etiologiaRESUMO
An 83-year-old woman was injured in a traffic accident. Enhanced computed tomography (CT) showed aortic injury on the isthmus, Stanford type A aortic dissection and intracranial hemorrhage. Neurological deficit was not noted. We immediately started to lower the blood pressure, and her hemodynamic status remained stable. Although intracranial bleeding had not worsened on the next day, a false lumen of the aortic arch was newly enhanced on CT. Emergency total arch replacement with frozen elephant trunk was performed under deep hypothermia and selective cerebral perfusion. Intraoperative angiography showed no endoleak at the descending aorta. Postoperative course was uneventful, and the patient was discharged on the 21st postoperative day. This procedure is useful for aortic injury involving the ascending aorta and the arch.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Idoso de 80 Anos ou mais , Dissecção Aórtica/cirurgia , Aorta , Aorta Torácica , Prótese Vascular , Feminino , Humanos , Stents , Resultado do TratamentoAssuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Prognóstico , Resultado do Tratamento , /uso terapêuticoRESUMO
The patient was 72-year-old man, who had old myocardial infarction, diabetes mellitus, dyslipidemia, hypertension and chronic obstructive pulmonary disease. He was complicated with congestive heart failure, and multi-vessel coronary artery disease and moderate aortic valve stenosis and regurgitation were diagnosed. We performed coronary artery bypass grafting(CABG) and aortic valve replacement. Intraoperative findings showed severe adhesions and tissue fibrosis around sternum. It was very difficult to dissect adhesions around left internal thoracic artery (LITA). LITA was injured, and great saphenous vein was anastomosed to left anterior descending coronary artery. Sternocostoclavicular hyperostosis was diagnosed on computed tomography( CT) findings such as remarkably thickened ster-num and adhesion of sternoclavicular joint. Postoperative course was complicated by osteomyelysis and necrosis of left side skin incision, for which omentopexy was needed. Sternocostoclavicular hyperostosis is rare disease, but we should recognize in preoperative evaluation.