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1.
J Immunol ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758119

RESUMEN

Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p = 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p = 0.024) and improving cancer-specific survival compared with the low group (p = 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38368501

RESUMEN

BACKGROUND: Immune editing, in which human leukocyte antigens (HLA) have critical roles, has been suggested to shape the landscape of human cancer. This study prospectively investigated whether HLA gene zygosity is associated with the prognosis of primary androgen deprivation therapy in advanced prostate cancer. METHODS: KYUCOG-1401-A was conducted in conjunction with a prospective clinical trial (KYUCOG-1401). Among the patients enrolled in KYUCOG-1401 and treated with primary androgen deprivation therapy, only Japanese patients were included. HLA genotypes of HLA-A, B, C, DRB1, DQB1, and DPB1 were determined. The effect of divergence of HLA genotypes on time to progression, prostate cancer-specific survival, and overall survival was evaluated. RESULTS: Among 127 patients, homozygosity for HLA-DRB1 (HR, 95% CI; 4.05, 1.54-10.7, P = 0.0047) and HLA-DQB1 (HR, 95% CI; 3.75, 1.47-9.58, P = 0.0058) was associated with an increased risk of prostate cancer-specific mortality. Patients with higher HLA evolutionary divergence scores at HLA-DQB1 (HR, 95% CI; 0.90, 0.82-0.97, P = 0.0093) had lower risks of prostate cancer-specific mortality. Androgen-responsive gene sets were upregulated in CD4low and CD8low tumors in the prostate cancer cohort, but not in the bladder and kidney cancer cohorts. CONCLUSIONS: This study suggested that the diversity of HLA-II loci including HLA-DRB1 and HLA-DQB1 plays an important role in advanced prostate cancer survival, contributing to improved risk stratification in advanced prostate cancer. Moreover, it was shown that CD4+ T cells play an important role in androgen deprivation therapy, suggesting that immunotherapy targeting CD4+ T cells is promising for prostate cancer.

3.
Int J Urol ; 31(5): 484-491, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38193650

RESUMEN

OBJECTIVE: Adrenocortical carcinoma is a rare condition, with limited comprehensive reports from Japan. This study aimed to review Japan's data on adrenocortical carcinoma by assessing information from 46 patients-with adrenocortical carcinoma across 10 Japanese university hospitals. METHODS: We conducted a retrospective multi-institutional analysis of the clinical characteristics of adrenocortical carcinoma in Japan. We evaluated data from 46 patients across 10 university hospitals over 10 years and analyzed the relationship between clinicopathological characteristics and overall survival. RESULTS: Five- and 10-year overall survival rates were 59% and 53%, respectively. Overall survival was significantly different among the tumor-node-metastasis system for adrenocortical carcinoma of the American Joint Committee on Cancer/International Union Against Cancer, with the worst prognosis in stage IV (p = 0.0044). In our cohort, neither the Weiss score nor the Ki-67 proliferation index correlated with overall survival. Adjuvant treatment did not yield improved overall survival, whereas resection of the primary tumor in stage IV disease was significantly associated with improved overall survival (p = 0.0262). Out of the cases evaluated for plasma hormones, plasma cortisol, aldosterone, testosterone, and DHEA-S levels were measured at 23%, 42%, 29%, and 62%, respectively, demonstrating higher levels than the upper normal limits. CONCLUSION: Patients with stage IV adrenocortical carcinoma had a poor prognosis; however, resection of the primary tumor in stage IV disease was associated with prolonged survival. The results of this study are expected to contribute to future treatment of adrenocortical carcinoma in Japan.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Carcinoma Corticosuprarrenal/patología , Carcinoma Corticosuprarrenal/mortalidad , Carcinoma Corticosuprarrenal/sangre , Masculino , Femenino , Japón/epidemiología , Persona de Mediana Edad , Neoplasias de la Corteza Suprarrenal/patología , Neoplasias de la Corteza Suprarrenal/mortalidad , Neoplasias de la Corteza Suprarrenal/sangre , Neoplasias de la Corteza Suprarrenal/terapia , Estudios Retrospectivos , Anciano , Adulto , Pronóstico , Tasa de Supervivencia , Hidrocortisona/sangre , Estadificación de Neoplasias , Adulto Joven , Testosterona/sangre , Sulfato de Deshidroepiandrosterona/sangre , Aldosterona/sangre , Adolescente , Anciano de 80 o más Años
4.
Med Mol Morphol ; 57(1): 68-75, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37991604

RESUMEN

Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.


Asunto(s)
Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Carcinoma Embrionario/metabolismo , Carcinoma Embrionario/patología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo
5.
Cancer Sci ; 115(1): 59-69, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37923388

RESUMEN

Sinus macrophages in draining lymph nodes (DLNs) are involved in anti-tumor immune reactions. CD169 (Sialoadhesin, Siglec-1) is expressed on sinus macrophages and is considered a surrogate marker for the immunostimulatory phenotype of macrophages. In this study, the significance of sinus macrophages in immunotherapy was evaluated using mouse models. Treatment with anti-programmed death-ligand 1 (PD-L1) antibody suppressed the subcutaneous tumor growth of MC38 and E0771 cells but was not effective against MB49 and LLC tumors. Decreased cytotoxic T-lymphocyte (CTL) infiltration in tumor tissues and CD169 expression in sinus macrophages were observed in MB49 and LLC cells compared to corresponding parameters in MC38 and E0771 cells. The anti-tumor effects of the anti-PD-L1 antibody on MC38 and E0771 cells were abolished when sinus macrophages in DLNs were depleted, suggesting that sinus macrophages are involved in the therapeutic effect of the anti-PD-L1 antibody. Naringin activated sinus macrophages. Naringin inhibited tumor growth in MB49- and LLC-bearing mice but did not affect that in MC38- and E0771-bearing mice. The infiltration of CTLs in tumor tissues and their activation were increased by naringin, and this effect was impaired when sinus macrophages were depleted. Combination therapy with naringin and anti-PD-L1 antibody suppressed MB49 tumor growth. In conclusion, CD169-positive sinus macrophages in DLNs are critical for anti-tumor immune responses, and naringin suppresses tumor growth by activating CD169-positive sinus macrophages and anti-tumor CTL responses. The activation status of sinus macrophages has been suggested to differ among tumor models, and this should be investigated in future studies.


Asunto(s)
Antineoplásicos , Neoplasias , Animales , Ratones , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Linfocitos T Citotóxicos/metabolismo , Anticuerpos/uso terapéutico , Inmunoterapia , Macrófagos/metabolismo , Antígeno B7-H1/metabolismo , Línea Celular Tumoral
6.
Int J Urol ; 31(4): 362-369, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38148124

RESUMEN

OBJECTIVES: To compare the effectiveness and safety of gonadotropin-releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone-sensitive prostate cancer (HSPC). METHODS: The study was conducted as KYUCOG-1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression-free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression-free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events. RESULTS: PSA progression-free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01-1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59-1.08, p = 0.146). No significant differences were observed in radiographic progression-free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A. CONCLUSIONS: The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Antagonistas de Andrógenos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Anilidas/efectos adversos , Nitrilos/efectos adversos , Compuestos de Tosilo/efectos adversos , Hormona Liberadora de Gonadotropina , Lípidos/uso terapéutico
7.
Int J Urol ; 30(9): 788-796, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37528632

RESUMEN

BACKGROUND: This study is part of the SNPs in Nivolumab PD-1 inhibitor for RCC (SNiP-RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. METHODS: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression-free survival (PFS), overall survival (OS), and treatment-related grade ≥ 3 (serious adverse events [SAEs]). RESULTS: We included 222 patients. The median age was 69 years (interquartile range 62-74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. CONCLUSION: The SNiP-RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Carcinoma de Células Renales/patología , Nivolumab/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/patología , Polimorfismo de Nucleótido Simple
8.
Cancer Diagn Progn ; 3(4): 522-527, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37405222

RESUMEN

BACKGROUND: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare RCC subtype, and FH-deficient RCC may be misdiagnosed as another type of RCC, such as type 2 papillary RCC or collecting duct carcinoma. FH and 2-succinocysteine (2SC) are useful diagnostic markers for FH-deficient RCC and can be measured using immunohistochemistry (IHC). CASE REPORT: A 30-year-old female with 3-month history of fatigue and left-flank mass was diagnosed with a 20×13×10 cm left-side renal mass with massive inferior vena cava (IVC) tumor thrombus that extended into the right atrium. She underwent nephrectomy and IVC thrombectomy, and a pathological diagnosis of type 2 papillary RCC was made. Four months after the surgery, computed tomography scan showed multiple liver metastases not observed immediately after surgery. Systemic treatment with sorafenib was initiated; however, she did not respond and died 3 months after treatment. Subsequent re-review of hematoxylin and eosin-stained sections indicated morphologic characteristics consistent with FH-deficient RCC, and IHC staining was negative for FH but positive for 2SC, indicating a diagnosis of FH-deficient RCC. Further immunological analyses revealed the loss of HLA-class I, b2 microglobulin, and HLA-DR antigens in cancer cells. In addition, a few CD8-positive cytotoxic T cells and CD163-positive tumor-associated macrophages were noted. CONCLUSION: An immunosuppressive tumor microenvironment that facilitates cancer immune evasion might be associated with the rapid progression and poor prognosis in our patient. Further investigation of the tumor immune microenvironment in patients with FH-deficient RCC is warranted.

9.
Mol Oncol ; 17(12): 2637-2658, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37452654

RESUMEN

Loss or downregulation of major histocompatibility complex class I (MHC-I) contributes to tumor immune evasion. We previously demonstrated that angiopoietin-like protein 2 (ANGPTL2) promotes tumor progression using a Xp11.2 translocation renal cell carcinoma (tRCC) mouse model. However, molecular mechanisms underlying ANGPTL2 tumor-promoting activity in the tRCC model remained unclear. Here, we report that ANGPTL2 deficiency in renal tubular epithelial cells slows tumor progression in the tRCC mouse model and promotes activated CD8+ T-cell infiltration of kidney tissues. We also found that Angptl2-deficient tumor cells show enhanced interferon γ-induced expression of MHC-I and increased susceptibility to CD8+ T-cell-mediated anti-tumor immune responses. Moreover, we provide evidence that the ANGPTL2-α5ß1 integrin pathway accelerates polycomb repressive complex 2-mediated repression of MHC-I expression in tumor cells. These findings suggest that ANGPTL2 signaling in tumor cells contributes to tumor immune evasion and that suppressing that signaling in tumor cells could serve as a potential strategy to facilitate tumor elimination by T-cell-mediated anti-tumor immunity.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Animales , Ratones , Proteína 2 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina/genética , Proteínas Similares a la Angiopoyetina/metabolismo , Escape del Tumor/genética , Represión Epigenética , Antígenos de Histocompatibilidad Clase I/genética , Carcinoma de Células Renales/genética , Modelos Animales de Enfermedad
10.
Jpn J Clin Oncol ; 53(9): 837-844, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37282601

RESUMEN

OBJECTIVES: To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. METHODS: We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. RESULTS: A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79-10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11-10.1; P = 0.0319) were identified as independent prognostic factors. CONCLUSIONS: The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.


Asunto(s)
Neoplasias del Pene , Masculino , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias del Pene/cirugía , Neoplasias del Pene/patología , Japón , Estadificación de Neoplasias , Resultado del Tratamiento
11.
Endocr Relat Cancer ; 30(7)2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37079309

RESUMEN

Androgen-deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events (AEs) vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (rPFS) at 1 year and AEs including de novo diabetes mellitus (DM), arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with rPFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival (OS) in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and OS in ADT. In addition, GWAS showed that several SNPs were associated with de novo DM, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADT-based combination therapies would make a valuable contribution to the development of personalized medicine.


Asunto(s)
Diabetes Mellitus , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Estudio de Asociación del Genoma Completo , Antagonistas de Andrógenos/uso terapéutico , Pronóstico , Diabetes Mellitus/tratamiento farmacológico
12.
IJU Case Rep ; 6(2): 147-149, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36874997

RESUMEN

Introduction: Dry mouth is the main symptom of sicca syndrome, which rarely occurs as an immune-related adverse event. Here we report a case of sicca syndrome caused by immune checkpoint inhibitor treatment. Case presentation: A 70-year-old man was diagnosed with left renal cell carcinoma after radical left nephrectomy. Nine years later, computed tomography revealed a metastatic nodule in the upper left lung lobe. Subsequently, ipilimumab and nivolumab were administered for recurrent disease. After 13 weeks of treatment, xerostomia and dysgeusia were noted. Salivary gland biopsy revealed lymphocyte and plasma cell infiltration in the salivary glands. Sicca syndrome was diagnosed and pilocarpine hydrochloride was prescribed without corticosteroids, with continuation of immune checkpoint inhibitor therapy. The symptoms alleviated after 36 weeks of treatment, with shrinkage of the metastatic lesions. Conclusion: We experienced sicca syndrome caused by immune checkpoint inhibitors. Sicca syndrome improved without steroids and the immunotherapy could be continued.

13.
Microbiol Immunol ; 67(7): 345-354, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36975091

RESUMEN

Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. By contrast, some immune-related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. This study investigated plasma cytokine, chemokine, and anti-CD74 autoantibody levels in patients with renal cell carcinoma (RCC) and analyzed their association with irAEs. In a discovery cohort of 13 patients, plasma levels of chemokine (C-X-C motif) ligand (CXCL) 1, IL-17A, IL-1ß, IL-6, IL-8, CXCL10, MCP-1, and TNFα were measured at baseline and post-dose 1. Only CXCL10, at post-dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (P = 0.0413). Plasma CXCL10 levels were then measured at baseline and post-dose 1 in an extended cohort of 43 patients with RCC who received ICI-based treatment. Higher plasma CXCL10 levels both at baseline and post-dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (P = 0.0246 and 0.0137, respectively). Plasma CXCL13 levels, which we measured in a previous study, were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post-dose 1 (P = 0.0037 and 0.052, respectively). No significant association between plasma anti-CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. In conclusion, plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on-treatment biomarker for irAEs.


Asunto(s)
Carcinoma de Células Renales , Quimiocina CXCL10 , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Humanos , Autoanticuerpos/uso terapéutico , Biomarcadores/sangre , Carcinoma de Células Renales/tratamiento farmacológico , Quimiocina CXCL10/sangre , Citocinas , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico
15.
Cancer Immunol Immunother ; 72(6): 1903-1915, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36729213

RESUMEN

BACKGROUND: Anti-PD-1 antibodies are widely used for cancer treatment including advanced renal cell carcinoma (RCC). However, their therapeutic and adverse effects vary among patients. This study aimed to identify genetic markers that predict outcome after nivolumab anti-PD-1 antibody treatment for advanced RCC. METHODS: This study was registered on the website of the University Hospital Medical Information Network (protocol ID, UMIN000037739). Patient enrollment was conducted at 23 institutions in Japan between August 19, 2019, and September 30, 2020. Patient follow-up ended on March 31, 2021. Patients were treated with nivolumab for advanced clear cell RCC. A genome-wide association study was performed in the development set, while genotyping of target regions in the validation set was undertaken. Single nucleotide polymorphisms (SNPs) in genes of interest CD274, PDCD1LG2 and PDCD1 were genotyped in the combined set. The primary endpoint was the association of SNPs with objective response following nivolumab treatment. As secondary endpoints, the associations of SNPs with radiographic progression-free survival (rPFS) and treatment-related grade ≥ 3 adverse events (AEs) were evaluated. RESULTS: A genome-wide association study followed by a validation study identified that SNPs in FARP1 (rs643896 and rs685736) were associated with objective response and rPFS but not AEs following nivolumab treatment. Furthermore, SNPs in PDCD1LG2 (rs822339 and rs1411262) were associated with objective response, rPFS, and AEs following nivolumab treatment. Genetic risk category determined according to the number of risk alleles in SNPs (rs643896 in FARP1 and rs4527932 in PDCD1LG2) excellently predicted objective response and rPFS in nivolumab treatment. CONCLUSION: This study revealed that SNPs in FARP1 and PDCD1LG2 were correlated with outcome in nivolumab treatment. The use of these SNPs may be beneficial in selecting appropriate treatment for individual patients and may contribute to personalized medicine.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Nivolumab/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Estudio de Asociación del Genoma Completo , Supervivencia sin Progresión , Polimorfismo de Nucleótido Simple , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética
16.
Cancer Med ; 12(7): 7859-7867, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36536528

RESUMEN

BACKGROUND: Management of pelvic node-positive prostate cancer has been challenging and controversial. We conducted a study to evaluate the outcomes of whole-pelvic (WP) simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT). METHODS: A total of 67 consecutive patients with cT1c-4N1M0 prostate cancer were definitively treated by WP SIB-IMRT. Neoadjuvant ADT (median: 8.3 months) was administered in all cases. WP SIB-IMRT was designed to simultaneously deliver 78, 66.3, and 58.5 Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes (LNs), and the pelvic LN region, respectively. Adjuvant ADT (median: 24.7 months) was administered in 66 patients. RESULTS: The median follow-up period was 81.6 months (range: 30.5-160.7). Biochemical relapse-free, overall, and prostate cancer-specific survival rates at 10 years were 59.8%, 79.6%, and 86.3%, respectively. Loco-regional recurrence was not observed. Being in International Society of Urological Pathology grade group 5 and having a posttreatment detectable nadir prostate-specific antigen (PSA) level (≥0.010 ng/ml) were significantly associated with worse prostate cancer-specific survival and progression of castration resistance. The 10-year cumulative incidence rates of grade 2 and 3 late toxicities were, respectively, 1.5% and 0% for genitourinary, 0% and 1.5% for gastrointestinal events. No grade 4 acute or late toxicities were observed. CONCLUSIONS: WP SIB-IMRT can be safely administered to patients with pelvic node-positive prostate cancer. Since grade group 5 and detectable nadir PSA levels are risks for castration resistance, we may need to increase the intensity of treatment for such cases.


Asunto(s)
Neoplasias Pélvicas , Neoplasias de la Próstata , Radioterapia de Intensidad Modulada , Masculino , Humanos , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Antagonistas de Andrógenos/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Metástasis Linfática , Recurrencia Local de Neoplasia
17.
Urol Case Rep ; 45: 102198, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36072283

RESUMEN

A 46-year-old man developed a right renal tumor with multiple lung and hilar lymph node metastases. Laparoscopic radical nephrectomy was performed, and clear cell renal cell carcinoma was diagnosed 6 years earlier. Despite the use of available systemic therapeutic agents, atelectasis in the right upper lobe due to a pulmonary hilar mass and brain metastases reduced his performance, and he was becoming terminally ill. After administration of avelumab plus axitinib as 9th-line therapy, significant shrinkage of the metastases and improvement in performance status were observed. This case indicates the possibility of using avelumab plus axitinib as late-line therapy.

18.
IJU Case Rep ; 5(5): 406-409, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36090927

RESUMEN

Introduction: Most seminal vesicle malignancies are secondary to prostate or bladder cancer. Herein, we report a case of primary clear cell carcinoma of the seminal vesicle. Case presentation: A 27-year-old man was referred to our department for hematospermia and macroscopic hematuria. A digital rectal examination showed a soft elastic prostatic mass. Cystoscopy showed no bladder abnormalities, and tumor marker tests were unremarkable. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a cystic tumor containing an enhanced nodule near the prostate and seminal vesicle. The tumor was removed en bloc with the prostate and seminal vesicle through a laparoscopic radical prostatectomy. A histopathologic examination confirmed the diagnosis, with the tumor likely arising from a remnant Müllerian epithelium. A 1-year follow-up revealed local tumor recurrence, prompting laparoscopy. Conclusion: A standard therapy for primary seminal vesicle carcinoma has not been established. Further studies are necessary to determine the optimal treatment strategy.

19.
IJU Case Rep ; 5(4): 281-285, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35795110

RESUMEN

Introduction: Subcapsular renal hematoma after ureterorenoscopy using a holmium yttrium-aluminum-garnet laser is a rare complication. We experienced a case of subcapsular hematoma after ureterorenoscopy. Case presentation: The patient was a 56-year-old man with a history of hypertension and coronary vasospastic angina, and he was taking antiplatelet drugs. He had the middle and lower calyx stones measured 36 mm in diameter of the right kidney. We performed ureterorenoscopy, which was completed about 2 h without intraoperative complications. We could not remove the stone completely. After the surgery, the patient developed a fever and complained of right back pain. Computed tomography showed several residual stones formed a stone street, obstructing the stent and resulting in grade 3 hydronephrosis. Furthermore, the right subcapsular renal hematoma infection had detected. Percutaneous hematoma drainage and percutaneous nephrostomy were performed. Conclusion: Subcapsular renal hematoma after ureterorenoscopy is an uncommon complication but should be kept in mind.

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