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1.
J Pak Med Assoc ; 73(5): 1137-1139, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37218255

RESUMO

Brain metastasis from testicular germ cell tumour (TGCT) is rare and represents only 2% of metastatic brain tumours. Although TGCTs have a good survival rate, the prognosis of brain metastasis is poor. Due to the rarity of the diagnosis, there are limited studies on the topic and a standardized treatment protocol does not exist. Surgical management has long been considered a positive prognostic factor; however, recent studies have investigated the impact of chemotherapy and radiotherapy in these patients. Current literature suggests multiplicity of brain lesions and treatment with chemotherapy or radiotherapy alone can have a poor impact on the prognosis of the disease. However, studies with larger cohorts are required to understand and develop the optimal treatment protocol for patients with brain metastasis from TGCT.


Assuntos
Neoplasias Encefálicas , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Análise de Sobrevida , Radioterapia , Antineoplásicos/uso terapêutico
2.
World J Urol ; 40(1): 119-126, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34599350

RESUMO

PURPOSE: To describe and compare differences in peri-operative outcomes of robot-assisted (RA-RPLND) and open (O-RPLND) retroperitoneal lymph node dissection performed by a single surgeon where chemotherapy is the standard initial treatment for Stage 2 or greater non-seminomatous germ cell tumour. METHODS: Review of a prospective database of all RA-RPLNDs (28 patients) and O-RPLNDs (72 patients) performed by a single surgeon from 2014 to 2020. Peri-operative outcomes were compared for patients having RA-RPLND to all O-RPLNDs and a matched cohort of patients having O-RPLND (20 patients). Further comparison was performed between all patients in the RA-RPLND group (21 patients) and matched O-RPLND group (18 patients) who had previous chemotherapy. RA-RPLND was performed for patients suitable for a unilateral template dissection. O-RPLND was performed prior to the introduction of RA-RPLND and for patients not suitable for RA-RPLND after its introduction. RESULTS: RA-RPLND showed improved peri-operative outcomes compared to the matched cohort of O-RPLND-median blood loss (50 versus 400 ml, p < 0.00001), operative duration (150 versus 195 min, p = 0.023) length-of-stay (1 versus 5 days, p < 0.00001) and anejaculation (0 versus 4, p = 0.0249). There was no statistical difference in complication rates. RA-RPLND had lower median lymph node yields although not significant (9 versus 13, p = 0.070). These improved peri-operative outcomes were also seen in the post-chemotherapy RA-RPLND versus O-RPLND analysis. There were no tumour recurrences seen in either group with median follow-up of 36 months and 60 months, respectively. CONCLUSIONS: Post-chemotherapy RA-RPLND may have decreased blood loss, operative duration, hospital length-of-stay and anejaculation rates in selected cases and should, therefore, be considered in selected patients. Differences in oncological outcomes require longer term follow-up.


Assuntos
Excisão de Linfonodo/métodos , Neoplasias Embrionárias de Células Germinativas/cirurgia , Procedimentos Cirúrgicos Robóticos , Neoplasias Testiculares/cirurgia , Terapia Combinada , Humanos , Metástase Linfática , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/secundário , Espaço Retroperitoneal , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/secundário , Resultado do Tratamento
4.
Int J Mol Sci ; 22(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34281219

RESUMO

The cure rate of germ cell tumours (GCTs) has significantly increased from the late 1970s since the introduction of cisplatin-based therapy, which to date remains the milestone for GCTs treatment. The exquisite cisplatin sensitivity has been mainly explained by the over-expression in GCTs of wild-type TP53 protein and the lack of TP53 somatic mutations; however, several other mechanisms seem to be involved, many of which remain still elusive. The findings about the role of TP53 in platinum-sensitivity and resistance, as well as the reported evidence of second cancers (SCs) in GCT patients treated only with surgery, suggesting a spectrum of cancer predisposing syndromes, highlight the need for a deepened understanding of the role of TP53 in GCTs. In the following report we explore the complex role of TP53 in GCTs cisplatin-sensitivity and resistance mechanisms, passing through several recent genomic studies, as well as its role in GCT patients with SCs, going through our experience of Center of reference for both GCTs and cancer predisposing syndromes.


Assuntos
Genes p53 , Neoplasias Embrionárias de Células Germinativas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/secundário , Proteína Supressora de Tumor p53/genética
5.
Urol Oncol ; 39(5): 303.e1-303.e8, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33685799

RESUMO

INTRODUCTION: Chemotherapy for testicular germ cell tumors (GCT) is highly effective, with few patients who do not respond. Clinical studies to evaluated novel treatments are challenging given the rarity of these patients. Therefore, we sought to evaluate PD-L1 staining on metastatic and postchemotherapy viable testicular GCTs as a surrogate for potential benefit for immunotherapy targeting the PD-1/PD-L1 axis. METHODS: Ethics research committee approval for this retrospective study was obtained by four participating institutions (CHU de Québec, St. Joseph's Health Care, Halifax Health Science Centre, Johannes Gutenberg University). Patients with viable metastatic testicular GCTs pathology samples were included. Patients with pure teratoma were excluded. PD-L1 staining with the 22C3 clone was evaluated on samples with >100 viable tumor cells using the combined positive score (CPS). RESULTS: From 51 patients identified at participating institutions, 24 postchemotherapy and 18 chemotherapy-naive metastatic samples were available for PD-L1 staining, with 9 matched prechemotherapy samples and 7 matched orchiectomy pathology samples, respectively. The median CPS score was 55.6 (IQR 16-100) for all metastatic samples, 44.9 (IQR 13-100) for postchemotherapy metastatic samples, and 68.8 (IQR 38-100) for chemotherapy-naïve metastatic samples, with the median number of viable tumor cells at 545, 500, and 550, respectively. Differences were not significant between chemotherapy-naïve and postchemotherapy samples (P = 0.07), though among non-seminoma GCT metastatic samples, CPS scores were significantly lower postchemotherapy (P = 0.02). Significant differences among postchemotherapy metastatic tumors were also seen according to predominant subtype, with lower CPS scores for predominant yolk sac and higher values for predominant seminoma and choriocarcinoma. In 7 patients with matched specimens pre- and postchemotherapy, a significant increase in CPS was observed for seminoma (26.7 vs. 81.7, P = 0.045), but not nonseminoma GCTs. Comparing all chemotherapy naïve-samples, PD-L1 expression was higher in metastatic samples versus testicular samples (mean CPS 68.8 vs. 39.8, P = 0.02). This was also seen in matched chemotherapy-naïve samples (mean CPS 77.9 vs. 33.1, P = 0.01). CONCLUSION: Our results suggest that most patients with refractory GCTs postchemotherapy will not benefit from PD-1/PD-L1 immunotherapy. However, the high PD-L1 expression in patients with predominant or pure seminoma post-chemotherapy suggests this may represent a subgroup for whom further trials may be considered.


Assuntos
Antígeno B7-H1/biossíntese , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/metabolismo , Adulto , Antígeno B7-H1/análise , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/química , Neoplasias Embrionárias de Células Germinativas/secundário , Estudos Retrospectivos , Neoplasias Testiculares/química , Neoplasias Testiculares/secundário , Adulto Jovem
6.
Technol Cancer Res Treat ; 20: 1533033820979702, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33455540

RESUMO

BACKGROUND: Testicular cancer represents the most common malignancy in young adult men. In the current study, we sought to analyze and compare the prognostic value of lymph node ratio (LNR) as well as positive lymph node counts (LNC) to understand its clinical significance in testicular germ cell tumors. METHODS: We employed eligibility criteria to recruit a total of 931 patients, with testicular cancer, from 2010 to 2015 from The Surveillance, Epidemiology, and End Results (SEER) database. We then used the X-Tile program to calculate LNR and LNC cutoff values and discriminate survival. We then calculated the overall and cancer specific survival rates and analyzed the association between LNR/LNC and clinical pathological characteristics using the χ2 test. Finally, we assessed the relationships between clinical pathological factors and patient survival using univariate Cox proportional hazard analysis. RESULTS: Univariate analysis revealed a significant association between prognosis with age (HR, 5.169; 95% CI, 1.758-15.200; P = 0.003), AJCC stage (III vs I: HR, 9.298; 95% CI, 2.691-32.131; P < 0.001), M stage (HR, 7.897; 95% CI, 3.417-18.251; P < 0.001) and LNR (HR, 3.009; 95% CI, 1.275-7.098; P = 0.012). On the other hand, LNC (HR, 1.743; 95% CI, 0.687-4.420; P = 0.242) was not significantly associated with prognosis. Analysis of the association between LNR/LNC and clinical pathological characteristics showed that high LNR patients tended to have significantly larger tumor sizes (χ2 = 7.877, P = 0.005), as well as advanced T (χ2 = 13.195, P = 0.004), N ( χ2 = 86.775, P < 0.001), M (χ2 = 19.948, P < 0.001) and 7th AJCC (χ2 = 103.074, P < 0.001) stages. In addition, high LNC patients were significantly associated with T (χ2 = 8.799, P = 0.032), N (χ2 = 74.390, P < 0.001) and 7th AJCC (χ2 = 111.759, P < 0.001) stages. CONCLUSION: LNR was a better predictor for long-term prognosis and was closely associated with clinical pathological characteristics than LNC in patients with testicular germ cell tumors.


Assuntos
Linfonodos/patologia , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/patologia , Adulto , Fatores Etários , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Programa de SEER , Taxa de Sobrevida , Neoplasias Testiculares/mortalidade , Carga Tumoral , Estados Unidos
8.
J Thorac Cardiovasc Surg ; 161(3): 856-868.e1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33478834

RESUMO

OBJECTIVE: Men with metastatic nonseminomatous germ cell tumors (NSGCTs) often present with residual chest tumors after chemotherapy. We examined the pathologic concordance of intrathoracic disease and outcomes based on the worst pathology of disease resected at first thoracic surgery. METHODS: A retrospective analysis was performed of consecutive patients undergoing thoracic resection for metastatic NSGCT in our institution between 2005 and 2018. RESULTS: Eighty-nine patients (all men) were included. The median age was 29 years (interquartile range [IQR], 23-35 years). Primary sites were testis (n = 84; 94.4%) and retroperitoneum (n = 5; 5.6%). Eighty-seven patients received chemotherapy before undergoing surgery. Nineteen patients (21.3%; group 1) had malignancy resected at first surgery (OR1), and the other 70 patients had benign disease at OR1 (78.7%; group 2). Concordant pathology between lungs was 85.2% in group 1 and 91% in group 2, and between lung and mediastinum was 50% in group 1 and 72.7% in group 2. Despite no teratoma at OR1, 3 patients (15.8%) in group 2 had resection of teratoma (n = 2) or malignancy (n = 1) at future surgery. After a mean follow-up of 65.5 months (IQR, 23.1-89.2 months) for group 1 and 47.7 months (IQR, 13.0-75.1 months) for group 2, overall survival was significantly worse for group 1 (68.4% vs 92.9%; P = .03). CONCLUSIONS: The wide range of pathology resected in patients with intrathoracic NSGCT metastases requires careful decision making regarding treatment. Pathologic concordance between lungs is better than that between lung and mediastinum in patients with intrathoracic NSGCT metastases. Aggressive surgical management should be considered for all residual disease due to the low concordance between sites and the potential for excellent long-term survival even in patients with chemotherapy-refractory disease.


Assuntos
Neoplasias Pulmonares/cirurgia , Neoplasias do Mediastino/cirurgia , Metastasectomia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/cirurgia , Procedimentos Cirúrgicos Torácicos , Adulto , Biópsia , Quimioterapia Adjuvante , Tomada de Decisão Clínica , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Neoplasias do Mediastino/mortalidade , Neoplasias do Mediastino/secundário , Metastasectomia/efeitos adversos , Metastasectomia/mortalidade , Terapia Neoadjuvante , Neoplasia Residual , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/secundário , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Procedimentos Cirúrgicos Torácicos/mortalidade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
J Cancer Res Clin Oncol ; 147(2): 533-538, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32772232

RESUMO

PURPOSE: Treatment of metastatic germ cell cancer (GCC) is based on the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic classification published in 1997. 5-year survival rates were reported to be 91%, 79%, and 48% for patients with good, intermediate and poor prognosis, respectively. However, treatment results may have improved over time due to cumulative experience, improved supportive care and modern-type chemotherapy. METHODS: Patients with metastatic GCC who received cisplatin-based chemotherapy at two institutions in Munich between 2000 and 2013 were retrospectively studied. Clinical characteristics, treatment and outcomes were analyzed with respect to the IGCCG prognostic classification. RESULTS: Of 225 patients (median age 35 years), 72 (32%) had seminoma (S) and 153 (68%) nonseminoma. 175 (78%), 30 (13%) and 20 patients (9%) had good, intermediate and poor prognosis according to the IGCCCG classification. The 2-year-progression free survival of patients with good, intermediate and poor prognosis was 91%, 83% and 37%, and the 5-year-overall survival (OS) was 98%, 96%, and 66%, respectively. There was no significant difference in the OS between patients in the good and intermediate prognosis group. CONCLUSION: Compared to data from the original IGCCCG classification system, the outcome of patients with metastatic GCC has considerably improved over time. While the prognosis of intermediate-risk patients is excellent, treatment in the poor-prognosis group remains to be improved.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/secundário , Estudos Retrospectivos , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Adulto Jovem
10.
Actas Urol Esp (Engl Ed) ; 45(1): 30-38, 2021.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33010987

RESUMO

INTRODUCTION AND OBJECTIVES: In this retrospective study, we aimed to evaluate lymph node (LN) density in retroperitoneal lymph node dissection (RPLND) to analyze whether residual mass after chemotherapy might behave as predicting factor for recurrence in patients with germ cell testicular cancer (GCTC). MATERIALS AND METHODS: The data of 185 patients that were operated between 12/2004 and 02/2017 because of GCTC were reviewed retrospectively. LN density was calculated. The patients were compared statistically in terms of demographic features, tumor characteristics, serum tumor marker levels, treatment strategies, and pathological results according to GCTC subtypes. Correlation analysis was performed to determine the parameters related to recurrent disease. RESULTS: The median follow-up was 79 (31-179) months and the median age of the patients was 23 (16-71). The median tumor size was 4 (1-18) cm. Five (2.7%) patients had metastatic disease at initial diagnosis. Seminoma, non-seminomatous-GCT and mix type-GCTC was detected in 62 (33.5%), 60 (32.4%) and 63 (34.1%) patients, respectively. Following inguinal orchiectomy, 48 (25.9%) patients underwent follow-up, 126 (68.1%) patients underwent chemotherapy and 11 (5.9%) patients underwent radiotherapy. A total of 21 (11.4%) patients underwent post-chemotherapy RPLND. Early and late recurrence was seen in 3 (1.6%) and 2 (1.1%) of the patients, respectively. A mild to moderate, negative, but significant correlation was found between the recurrence and the number of LNs containing metastatic deposits and LN density (r= -0.490, P=.024 and r= -0.450, P=.041, respectively). CONCLUSIONS: There was a negative correlation between the number of LNs containing metastatic deposits and LN density and recurrent disease.


Assuntos
Linfonodos/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/cirurgia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Seguimentos , Humanos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Embrionárias de Células Germinativas/secundário , Valor Preditivo dos Testes , Espaço Retroperitoneal , Estudos Retrospectivos , Centros de Atenção Terciária , Neoplasias Testiculares/patologia , Neoplasias Testiculares/secundário , Fatores de Tempo , Adulto Jovem
12.
Ann Thorac Surg ; 111(4): 1141-1149, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32882201

RESUMO

BACKGROUND: Outcomes after thoracic metastasectomy in patients with testicular germ cell tumors (GCTs) who received first-line chemotherapy alone versus salvage chemotherapy remain unexplored. METHODS: We conducted a retrospective review of patients who underwent thoracic metastasectomy for residual GCT between 1997 and 2019 at a single tertiary center. Factors associated with progression-free survival (PFS) and overall survival (OS) were assessed using multivariable Cox regression. RESULTS: Of 251 patients, 191 received only first-line chemotherapy (76%) and 60 received salvage chemotherapy (24%). Median follow-up was 3.45 years (interquartile range, 1-7.93 years). Among first-line patients without teratoma in the primary tumor, with necrosis in the retroperitoneal nodes and normalized or decreasing serum tumor markers, 17 of 20 had intrathoracic necrosis (85%). Among first-line and salvage patients, respectively, 5-year OS was 93% (95% confidence interval [CI], 89%-98%) versus 63% (95% CI, 51%-78%; P < .001), and 5-year PFS was 69% (95% CI, 62%-77%) versus 40% (95% CI, 29%-56%; P < .001). On multivariable analysis, multiple lung lesions (hazard ratio [HR] = 3.01; 95% CI, 1.50-6.05; P = .002) and brain metastasis (HR = 4.51; 95% CI, 2.34-8.73; P < .001) at diagnosis, salvage chemotherapy (HR = 1.85; 95% CI, 1.10-3.13; P = .021), teratoma (HR = 2.68; 95% CI, 1.50-4.78; P = .001), and viable malignancy (HR = 4.34; 95% CI, 2.44-7.71; P < .001) were associated with worse PFS. CONCLUSIONS: Although GCT patients treated with salvage chemotherapy followed by thoracic metastasectomy have more aggressive disease and poorer PFS, they can achieve encouraging OS. Our findings highlight the integral role of aggressive thoracic metastasectomy in the treatment of GCT patients with residual thoracic disease after first line-only or salvage chemotherapy.


Assuntos
Metastasectomia/métodos , Estadiamento de Neoplasias/métodos , Neoplasias Embrionárias de Células Germinativas/terapia , Terapia de Salvação/métodos , Neoplasias Testiculares/terapia , Procedimentos Cirúrgicos Torácicos/métodos , Adulto , Intervalo Livre de Doença , Humanos , Linfonodos/patologia , Masculino , Metástase Neoplásica , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/secundário , Prognóstico , Estudos Retrospectivos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/secundário , Adulto Jovem
13.
World J Urol ; 39(6): 1977-1984, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32797261

RESUMO

PURPOSE: To compare perioperative outcomes and perform the first cost analysis between open retroperitoneal lymph node dissection (O-RPLND) and Robotic-RPLND (R-RPLND) using a national all-payer inpatient care database. METHODS: Nationwide Inpatient Sample (NIS) was queried between 2013-2016 for primary RPLND and germ cell tumor. We compared cost, length of stay (LOS), and complications between O-RPLND and R-RPLND. Linear regression plots identified point of cost equivalence between R-RPLND and O-RPLND. A multivariable linear regression model was generated to analyze predictors of cost. RESULTS: 44 cases of R-RPLND and 319 cases of O-RPLND were identified. R-RPLND was associated with lower rate of complications (0% vs. 16.6%, p < 0.01) and shorter LOS [Median (IQR): 1.5 (1-3) days vs. 4 (3-6) days, p < 0.01]. Rates of ileus, genitourinary complications, and transfusions were lower with R-RPLND, but did not reach significance. On multivariable analysis, robotic approach independently contributed $4457, while each day of hospitalization contributed to an additional $2,431 to the overall model of cost. Linear regression plots determined point of cost equivalence between an R-RPLND staying a mean of 2 days was 4-5 days for O-RPLND, supporting the multivariable analysis. Total hospitalization cost was equivalent between R-RPLND and O-RPLND [Median (IQR): $15,681($12,735-$21,596) vs $16,718($11,799-$24,403), p = 0.48]-suggesting that the cost equivalency of R-RPLND is, at least in part, attributable to shorter LOS. CONCLUSION: While O-RPLND remains the gold standard and this study is limited by selection bias of a robotic approach to RPLND, our findings suggest primary R-RPLND may represent a cost-equivalent option with decreased hospital LOS in select cases.


Assuntos
Custos e Análise de Custo , Custos de Cuidados de Saúde , Excisão de Linfonodo/economia , Excisão de Linfonodo/métodos , Neoplasias Embrionárias de Células Germinativas/cirurgia , Procedimentos Cirúrgicos Robóticos/economia , Neoplasias Testiculares/cirurgia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Embrionárias de Células Germinativas/secundário , Espaço Retroperitoneal , Neoplasias Testiculares/patologia , Resultado do Tratamento
14.
Cancer Med ; 10(1): 156-163, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135391

RESUMO

PURPOSE: Germ cell tumors (GCTs) are cured with therapy based on cisplatin, although a clinically significant number of patients are refractory and die of progressive disease. Based on preclinical studies indicating that refractory testicular GCTs are hypersensitive to hypomethylating agents (HMAs), we conducted a phase I trial combining the next-generation HMA guadecitabine (SGI-110) with cisplatin in recurrent, cisplatin-resistant GCT patients. METHODS: Patients with metastatic GCTs were treated for five consecutive days with guadecitabine followed by cisplatin on day 8, for a 28-day cycle for up to six cycles. The primary endpoint was safety and toxicity including dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). RESULTS: The number of patients enrolled was 14. The majority of patients were heavily pretreated. MTD was determined to be 30 mg/m2 guadecitabine followed by 100 mg/m2 cisplatin. The major DLTs were neutropenia and thrombocytopenia. Three patients had partial responses by RECIST criteria, two of these patients, including one with primary mediastinal disease, completed the study and qualified as complete responses by serum tumor marker criteria with sustained remissions of 5 and 13 months and survival of 16 and 26 months, respectively. The overall response rate was 23%. Three patients also had stable disease indicating a clinical benefit rate of 46%. CONCLUSIONS: The combination of guadecitabine and cisplatin was tolerable and demonstrated activity in patients with platinum refractory germ cell cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/análogos & derivados , Cisplatino/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/efeitos adversos , Azacitidina/uso terapêutico , Cisplatino/efeitos adversos , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Humanos , Indiana , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Mod Pathol ; 34(4): 834-841, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33319858

RESUMO

Pathological risk factors for metastatic disease in patients with testicular non-seminomatous germ cell tumors are debated. The tumor-node-metastasis (TNM) classification eighth edition for testicular cancers includes divergent versions, by the International Union Against Cancer (UICC) and by the American Joint Committee for cancer (AJCC). We investigated pathological predictors of metastatic disease at presentation in 219 non-seminomatous germ cell tumors with reference to both classifications. Age, tumor size, percentage of embryonal carcinoma, lymphovascular invasion, invasion of stromal rete testis, hilar soft tissue, epididymis, spermatic cord, and tunica vaginalis, as well as tumor at spermatic cord margin, were assessed and correlated with clinical stage at presentation. Of the 219 NSGCT cases, 151 (69%) were clinical stage I, 68 (31%) were clinical stage II/III. On univariate analysis, tumor size (P = 0.028), percentage of embryonal carcinoma (P = 0.004), lymphovascular invasion (P = 0.001), stromal rete testis invasion (P = 0.001), hilar soft tissue invasion (P = 0.010), epididymis invasion (P = 0.010), direct spermatic cord invasion (P = 0.001), and tumor at spermatic cord margin ((P = 0.009) were associated with higher clinical stage. On multivariate analysis, lymphovascular invasion (P = 0.003), tumor size (P = 0.005), percentage of embryonal carcinoma (P = 0.005), stromal rete testis invasion (P = 0.008) remained significant. A tumor size of 6 cm and an embryonal carcinoma percentage of 70% were the significant cut-off values. We conclude that in addition to lymphovascular invasion, stromal rete testis invasion, tumor size, and embryonal carcinoma percentage are strong predictors of metastatic disease at presentation and their inclusion should be considered in any future TNM revision. Further, our results support the changes in the AJCC TNM eighth edition as invasion of the epididymis and hilar soft tissue were both univariately significant.


Assuntos
Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/patologia , Adulto , Bases de Dados Factuais , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/terapia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Neoplasias Testiculares/terapia , Carga Tumoral
17.
Urol Oncol ; 39(2): 136.e11-136.e17, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33308971

RESUMO

BACKGROUND: Approximately 70% to 80% of patients with metastatic nonseminomatous germ cell tumor (NSGCT) treated with cisplatin-based chemotherapy achieve a complete response, defined as normalization of serum tumor markers and either no residual retroperitoneal mass (RRM) or an RRM <1.0 cm. While there is universal agreement that patients with an RRM ≥1.0 cm should undergo retroperitoneal lymph node dissection (RPLND), many institutions including ours recommend surveillance for patients who achieve a complete response. However, studies have not defined which axis of the RRM should be considered when deciding between surveillance and RPLND. PATIENTS AND METHODS: Good-risk metastatic NSGCT patients treated with cisplatin-based chemotherapy who achieved a complete response and underwent surveillance were identified using our institution's electronic medical records. A post-hoc review was performed by a blinded radiologist. The RRM dimensions in the transaxial short axis (TSA), transaxial long axis (TLA), and craniocaudal axis (CCA) were recorded. Differences in the frequency of recurrence between groups with an RRM <1.0 cm and ≥1.0 cm in the TLA and CCA were assessed using the Fisher exact test. RESULTS: Thirty-nine patients who met study criteria were included. At a median follow-up of 63.8 months, 2 patients (5.1%) recurred. Both were successfully treated with salvage chemotherapy and RPLND. Thirteen (33%) and 27 (69%) patients had an RRM ≥1.0 cm in the TLA and CCA, respectively. There were no statistically significant differences in the risk of recurrence between patients with an RRM <1.0 cm and ≥1.0 cm in the TLA (P = 0.54) or CCA (P = 0.53). CONCLUSIONS: Surveillance is an effective strategy in good-risk NSGCT patients with a postchemotherapy RRM <1.0 cm in the TSA. Our study suggests referencing the TSA and not the TLA or CCA may avoid unnecessary postchemotherapy RPLNDs.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Retroperitoneais/secundário , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/secundário , Adolescente , Idoso , História do Século XVI , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Vigilância da População , Estudos Retrospectivos , Adulto Jovem
18.
BMJ Case Rep ; 13(11)2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203785

RESUMO

Germ cell tumours (GCT) are the most common testicular neoplasms, seen mainly in young adults. Rarely they can affect extragonadal tissues, either as primary tumours or as metastases, most commonly to retroperitoneal lymph nodes. A 'burned-out' testicular tumour is a metastatic GCT with a relatively occult primary testicular tumour, which has histologically spontaneously regressed. We report a case of a 26-year-old man who presented with an acute history of lower back pain and leg swelling. CT demonstrated a large retroperitoneal soft tissue mass causing right-sided hydronephrosis with inferior vena cava and iliofemoral vein thrombosis. Although clinical examination of the testis was normal, ultrasound imaging of the scrotum identified a burned-out testicular primary. Orchiectomy confirmed the diagnosis and the patient responded well to chemotherapy, with no viable residual tumour on follow-up imaging. However, despite nephrostomy insertion, a dimercaptosuccinic acid (DMSA) scan demonstrated loss of function of the right kidney after treatment.


Assuntos
Neoplasias Embrionárias de Células Germinativas/secundário , Espaço Retroperitoneal/diagnóstico por imagem , Neoplasias Testiculares/patologia , Veia Cava Inferior/patologia , Adulto , Tratamento Farmacológico/métodos , Humanos , Hidronefrose/etiologia , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Primárias Desconhecidas/patologia , Orquiectomia/métodos , Espaço Retroperitoneal/patologia , Escroto/diagnóstico por imagem , Escroto/patologia , Neoplasias de Tecidos Moles/complicações , Síndrome , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/embriologia , Neoplasias Testiculares/secundário , Neoplasias Testiculares/cirurgia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Ultrassonografia/métodos , Trombose Venosa/etiologia
19.
BMC Surg ; 20(1): 272, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160340

RESUMO

BACKGROUND: Metastatic germ cell cancer of the testis is characterized by favorable prognosis since effective treatment methods are available even in cases of extensive disease. Retroperitoneal masses frequently encroach major blood vessels requiring a vascular intervention usually performed in association with the post-chemotherapy retroperitoneal lymph node dissection (RPLND). Reported clinical case describes a successful pre-treatment endovascular surgery for abdominal aortic rupture allowing for full-dose systemic chemotherapy administration, and subsequent radical surgical intervention at primary tumor site as well as metastatic retroperitoneal lymph node dissection including the reconstruction of inferior caval vein. CASE PRESENTATION: Patient presented with left-sided testicular tumor and voluminous retroperitoneal mass with vascular involvement. Soon after the patient had been admitted for the first cycle of cisplatin-based chemotherapy, computed tomographic angiography (CTA) revealed a dorsal aortic wall rupture with active extravasation and irregular pseudoaneurysmatic dilatation of the aorta below the leak area. Retroperitoneal intratumoral hemorrhage associated with the bilateral iliac venous thrombosis required an endovascular repair procedure of infrarenal abdominal aorta. CONCLUSIONS: Following the successful endovascular aortic repair 3 cycles of BEP (bleomycin, etoposide, cisplatin) regimen were administered with subsequent delayed left radical orchiectomy and RPLND associated with vena cava inferior (VCI) resection. Reconstruction of VCI was originally not deemed necessary as collateral blood flow appeared sufficient, however, intraoperative complications resulted in the need for unilateral VCI reconstruction, using the interposed bypass between right common iliac vein and infrarenal segment of VCI. Histopathologic examination of the attained specimen detected no vital cancer structures. The patient remains disease-free 18 months after the RPLND.


Assuntos
Ruptura Aórtica/cirurgia , Procedimentos Endovasculares/métodos , Hemorragia/cirurgia , Neoplasias Embrionárias de Células Germinativas , Neoplasias Retroperitoneais , Neoplasias Testiculares , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Aorta Abdominal/cirurgia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/etiologia , Ruptura Aórtica/patologia , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Angiografia por Tomografia Computadorizada , Etoposídeo/administração & dosagem , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Veia Ilíaca , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/secundário , Neoplasias Retroperitoneais/cirurgia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/secundário , Neoplasias Vasculares/cirurgia , Veia Cava Inferior/cirurgia , Trombose Venosa/cirurgia
20.
Bull Cancer ; 107(5S): S41-S48, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32620206

RESUMO

More than 80 % of patient with metastatic germ cell tumor are cured with first line chemotherapy. Twenty to 30 % of patients will experience relapse or refractory disease with a very poor long-term prognosis. Most of them had metastatic germ cell tumors with a poor prognosis according to the international germ cell classification collaborative group (IGCCCG). The role of treatment intensification by high dose chemotherapy (HDCT) followed by stem cell rescue has not been demonstrated yet in the first line setting compared to standard chemotherapy. The role of HDCT in first or second salvage is also not yet demonstrated, many studies have been published in this situation with a lot of different regimen. Outside clinical trial, HDCT remains an option in salvage therapy, depending on many factors including prognostics factors, previous therapy, general condition and reference center consideration to select eligible patient who could benefit the most of this approach. Results from the international randomized trial TIGER will provide evidence-based information for HDCT strategy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Humanos , Neoplasias Embrionárias de Células Germinativas/secundário , Terapia de Salvação
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