Genome damage in testicular seminoma patients seven years after radiotherapy

Abstract

Purpose: Testicular seminoma cancer incidence has significantly increased over the last few decades, and although it is successfully treated by radiotherapy, long-term health risks are still unclear. The aim of the study was to show long-term genome damage in patients with seminoma after radiotherapy.

Materials and methods: Chromosome aberration (CA) and micronucleus (MN) assays seven years after radiotherapy with a total dose of 25 Gy were conducted in 10 testicular seminoma patients aged 23–49 years and results were compared with 10 healthy control subjects matched for age and smoking status.

Results: Although mean CA frequency did not deviate from control values, significantly increased frequencies of dicentrics, double minutes, and ring chromosomes were detected in seminoma patients. MN frequency in binuclear lymphocytes of patients was similar to controls (4.60/1000 vs. 5.82/1000, respectively). Significantly higher MN frequency was detected in mononuclear lymphocytes of patients than in controls (2.55/1000 vs. 0.73/1000, respectively). Average percentage of centromere-positive MN was 62.6% in seminoma patients.

Conclusion: This study shows the persistence of unstable CA in seminoma patients seven years after radiotherapy and the relevance of long-term follow up. MN frequency in mononuclear lymphocytes was shown to be relevant biomarker of long-term genome damage.     

The effect of radiotherapy treatment changes on sites of relapse in stage I testicular seminoma

AIM: To evaluate relapse patterns in stage I testicular seminoma related to changes in radiotherapy practice.METHOD: Four hundred and six patients with stage I testicular seminoma were treated with adjuvant radiotherapy following orchidectomy: 338 patients received para-aortic radiotherapy only and 68 patients with added risk factors had radiotherapy extended to include the pelvis. Computed tomograms of relapsed patients were reviewed and sites of relapse were documented with correlation to the radiotherapy field. RESULTS: Thirteen relapses were identified; 10 occurring in the para-aortic radiotherapy group (3.0% relapse rate) and three in the extended radiotherapy field group (4.4% relapse rate). Sites of relapse were; five pelvis, three mediastinum, one lung, one scapula, one scrotum, while one patient had multiple relapse sites including the pelvis and one had a tumour marker relapse with no site identified. All the pelvic relapses occurred in the para-aortic radiotherapy group. CONCLUSION: Pelvic relapse only occurred when radiotherapy had been confined to the para-aortic region. Since para-aortic radiotherapy achieves equivalent outcome to wider field radiotherapy with reduced toxicity, it is likely to become standard practice in stage I seminoma and pelvic relapses will therefore increase in frequency. It is therefore important to include pelvic imaging when relapse is suspected.     

The role of bipedal lymphangiography in testicular seminoma

Determining the extent of intra-abdominal spread of testicular seminoma by radiographic studies is an essential step in planning rational treatment following orchidectomy. CT scanning is generally accepted as being superior to lymphangiography in assessing the retroperitoneal space. We reviewed the relative contribution of these two procedures in a retrospective analysis of 73 consecutive patients with testicular seminoma managed at Westmead Hospital between January 1980 and September 1987. Abdominal CT scans and bipedal lymphangiography (LAG) were carried out in 72 and 51 patients respectively, 50 patients undergoing both procedures. We found concordance between the two techniques to be 88%. Upstaging occurred in 5 patients using CT (10%), 7 patients using LAG (14%), and in 8 patients (16%) when both tests were utilised. Four patients were upstaged by both techniques while the remaining 4 patients were upstaged using one technique alone. Serum beta-HCG was not a reliable screen for residual disease. Residual disease in the few patients with an elevated serum beta-HCG was easily detected by CT scanning. We conclude that there is a continuing role for LAG in assessing patients with clinical Stage I seminoma when the abdominal CT scan is equivocal or normal.     

Immobilization and stabilization of testicular clamshell shields in seminoma patients.

It is standard practice when treating the pelvic and para-aortic lymph nodes of seminoma patients, to use a method to reduce the dose to the testicles due to scattered radiation. A common method is the use of lead testicular shields (clamshells). We have developed a method of immobilizing the patient while at the same time providing a stable and reproducible position for the testicular shield.     

The usefulness of gallium-67 citrate scanning in testicular seminoma

An analysis of 77 consecutive patients with a histologic diagnosis of seminoma testis, assessed and treated at the Cross Cancer Institute between 1977 and 1982, is presented. Ga-67 citrate was first used in the assessment of patients with malignant testicular tumors in 1973. Following three years of study that supported the observation of the gallium-avid nature of seminoma, gallium scans became routine in the initial staging assessment and were used also when recurrence was suspected. From 1977 through 1982, 72 patients with biopsy-proven seminoma testis were assessed initially for extent of disease by Ga-67 scanning. Comparison with intravenous pyelography and bipedal lymphography was possible for accuracy of tumor assessment. The scan sensitivity was 83%, and the specificity was 95%. During the same period, gallium was studied in nonseminomatous testicular tumors but the results were disappointing and its use was discontinued. The gallium-avid nature of seminoma testis may be useful in determining the extent of disease.     

天冬氨酸转氨酶与中性粒细胞比值对肝癌患者TACE治疗预后的影响

目的 探讨经导管肝动脉化疗栓塞(TACE)术前血清天冬氨酸转氨酶(AST)和中性粒细胞比值(ANRI)对肝细胞肝癌患者预后的评估价值.方法 收集2008年1月至2011年6月期间107例肝细胞肝癌患者的临床资料,研究对象均成功施行TACE,以5年总生存率绘制ROC曲线确定截断值,对术前患者的ANRI、AST与淋巴细胞比值(ALRI)、AST与血小板计数比值(APRI)、中性粒细胞与淋巴细胞比值(NLR)、血小板计数与淋巴细胞比值(PLR)及其他临床病理参数进行单因素、多因素Logisitc回归分析及Kaplan-Meier生存分析,以确定上述因素对无病生存期(DFS)和生存期(0S)的预测价值.结果 ANRI与HBsAg、AST、肝硬化的存在、肿瘤大小、门静脉癌栓及肿瘤的复发具有相关性(P＜0.05).通过单因素分析显示,ANRI、ALRI、APRI、NLR、PLR与接受TACE治疗肝癌患者的DFS和OS具有显著相关性(P＜0.05).多因素Logisitc回归分析显示,ANRI被证明是该类患者DFS和OS的独立影响因素(P＜0.05).Kaplan-Meier生存分析表明,术前ANRI＞7.8的患者行TACE治疗后预后较差.结论 TACE术前ANRI水平是肝细胞肝癌患者预后独立的预测因素,ANRI水平较高往往提示该类患者行TACE治疗的预后较差.     

Late relapse of testicular seminoma in the posterior mediastinum

Patients with testicular seminoma are usually cured if they survive disease-free for 5 years after therapy. Late relapse can also occur but is rare. In particular, relapse of testicular seminoma in the form of a large mediastinal mass is extremely rare. We present here a 37-year-old man with a late relapse of a large testicular seminoma in the posterior mediastinum, encasing the descending thoracic aorta, and compressing the left atrium and left main bronchus on computed tomography (CT) and positron emission tomography (PET).     

'Watch policy' in patients with suspected stage I testicular seminoma: CT as a sole staging and surveillance technique

A study was undertaken to assess the role of computed tomography (CT) as the sole imaging technique for the staging and surveillance of patients with stage I testicular seminoma. Of the 15 patients studied, five (33%) relapsed. This relapse rate differs from other studies. The reasons for this are discussed.     

Association of genetic variants in VEGF-A with clinical recurrence in prostate cancer patients treated with definitive radiotherapy

Background and purpose

Vascular endothelial growth factor-A (VEGF-A), a key regulator of tumor-induced angiogenesis, is critical for tumor growth and metastasization. The goal of the present study was to evaluate the prognostic value of VEGF single nucleotide polymorphisms (SNPs) and haplotypes for clinical recurrence after definitive radiotherapy for prostate cancer.

Patients and methods

The association of seven VEGF-A polymorphisms and their haplotypes with clinical recurrence (defined as the occurrence of local recurrence and/or distant metastases) in 496 prostate cancer patients treated with definitive radiotherapy were investigated. Genotypes were determined by 5’-nuclease (TaqMan) assays; haplotypes were analyzed using the Haploview program.

Results

Within a median follow-up time of 80 months, 44 patients (9?%) developed clinical recurrences. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms (??2578C > A, ??2489C > T, ??1498C > T, ??634G > C, ??7C > T) upstream of the coding sequence (CCCCC, ATTGC, CCCGC, ATTGT) and two polymorphisms (936C > T, 1612G > A) downstream of the coding sequence (CA, CG, TG). Carriers of at least 1 copy of the ATTGC haplotype were at higher risk of recurrence (hazard ratio [HR] 3.83; 95?%CI 1.48–9.90, p?=?0.006); for carriers of 2 copies, the HR was 4.85 (95?%CI 1.72–13.6; p?=?0.003). In multivariate analysis, patients harboring at least one copy of the ATTGC haplotype remained at increased risk of recurrence (HR 3.63, 95?%CI 1.38–9.55, p?=?0.009); in patients carrying 2 copies, the HR was 4.72 (95?%CI 1.64–13.6, p?=?0.004).

Conclusion

Our findings indicate that the VEGF-A ATTGC haplotype may predict clinical recurrence in prostate cancer patients treated with radiotherapy.     

Role of radiotherapy in the treatment of seminoma of the testis

From 1965 through 1988, 113 patients affected with testicular seminoma were treated at the Dept. of Radiotherapy, University "La Sapienza", Rome, Italy. Mean age of the patients was 38 years; in 70 cases tumor developed in the right testis and in 43 in the left one. In 9 patients underlying cryptorchidism was observed. All cases underwent radical orchiectomy. Histology diagnosed anaplastic seminoma in 5 cases and pure seminoma in all the other patients. Structures were involved in 7 cases. Eighty-four patients were in stage I, 20 in stage IIA, 4 in IIB, 4 in IIIA, and 1 in stage IIIB. All patients staged as I and IIA were treated with exclusive radiotherapy on paraaortic lymph nodes and inguinal and iliac lymph nodes of the involved sites (total doses: 28-35 Gy in stage I and 34-40 Gy in stage IIA). Before 1970 these patients underwent prophylactic irradiation of mediastinum and of left supraclavicular lymph nodes (total dose: 25-28 Gy). Patients in stage IIB were administered subdiaphragmatic lymph nodes irradiation with inverted-Y field (total dose: 36-45 Gy). Two cases were irradiated also on mediastinum and left supraclavicular lymph nodes, and 2 received two cycles of polychemotherapy (PVB) before irradiation. Patients in stage IIIA underwent sub-/supra-diaphragmatic irradiation (total dose: 40-45 Gy, and 40-42 Gy). The case in stage IIIB underwent palliation chemotherapy and local irradiation. All cases in stages I, IIA and IIB obtained complete remission. Three cases of the 4 in stage IIIA obtained complete remission (75%), while 1 (25%) progressed and died 8 months after diagnosis; the only case in stage IIIB progressed and died after 7 months of follow-up. Two cases in stage I recurred (2.4%), 1 in the mediastinum and 1 in the left supraclavicular lymph nodes. Both were cured with salvage radiation therapy. Toxicity related to treatment was low. Two cases in stage I developed secondary malignant neoplasms, at 4 and 34 months of follow-up, respectively.     

Early results of exclusive radiotherapy in advanced stage cervical carcinoma performed with reference to ICRU Report 38.

BACKGROUND AND PURPOSE: Most of the studies in which medium dose rate (MDR) or high dose rate (HDR) brachytherapy have been used for the treatment of cervical carcinoma were prescribed according to the Manchester system. This study aims to present early results of exclusive radiotherapy, which includes MDR brachytherapy, performed using ICRU 38 recommendations to their full extent. MATERIALS AND METHODS: Between 1994 and 1997, 80 patients with advanced stage (FIGO stages IIA-IVA) cervical carcinoma received external beam therapy (EBT) to the pelvis at a total dose of 46 to 50 Gy and two fractions of MDR (approximately 11.5 Gy/h) brachytherapy delivered to the 60 Gy reference isodose. A dose correction factor of 0.80 was used for dose rate effect. Additionally, 10-14 Gy EBT was given as a parametrial boost. Mean follow-up duration was 25.7 months. RESULTS: Local control (LC) and 3-year overall survival were 63% and 68%, respectively, for all patients. For stages II, III, and IV, LC was 75%, 44%, and 60% and 3-year survival was 75%, 62%, and 50%, respectively. Seven patients had severe late complications (8.7%). CONCLUSIONS: The results of this study encourage the use of ICRU 38 recommendations with MDR or HDR brachytherapy with some additional measures in terms of the radiobiological aspect.     

Bone marrow transplantation in patients with multiple myeloma: prognostic significance of MR imaging

OBJECTIVE. This study in myeloma patients treated with myeloablative therapy and bone marrow transplantation assessed the prognostic value of MR imaging before and after treatment of the bone marrow and the prognostic value of an index reflecting changes on MR images obtained before and after treatment. SUBJECTS AND METHODS. MR images (T1-weighted images before and after injection of gadolinium and T2(*)-weighted images) of the spine and pelvis were obtained 1 month before and 1 month after marrow transplantation in 25 consecutive patients with stage III myeloma. Pre- and posttreatment MR imaging patterns of marrow involvement (normal, focal, diffuse), number of focal lesions, and a "marrow evolution index" (0-8 on the basis of comparison of the lesions [number, size, contrast enhancement] and of the surrounding marrow background on pre- and posttreatment MR images) were determined. Hematologic and MR imaging parameters were correlated with the quality of response to treatment (complete versus partial remission) and with relapse-free and overall survival. RESULTS. Response quality did not differ among categories of patients determined on the basis of MR images. Individual MR imaging parameters did not correlate with response duration and survival. Patients with a low marrow evolution index had significantly longer relapse-free (p < 10(-3)) and overall survival (p = 0.005) than patients with a high index. CONCLUSION. Individual MR imaging parameters before and after treatment had no prognostic significance in our series of myeloma patients treated with marrow transplantation. Comparison of MR images before and after treatment using a marrow evolution index may help predict response duration and survival.     

373例食管癌患者三维技术放疗预后分析

目的 观察对食管癌患者采用三维技术放疗的长期疗效,并分析预后影响因素。方法 回顾性分析接受三维技术放疗食管鳞癌患者373例。其中三维适形放疗（3D-CRT）231例,调强放疗（IMRT）142例;单纯放疗202例,放化疗联合171例;累及野（IFI）照射249例,选择性淋巴引流区预防（ENI）照射124例;根治量50~60 Gy者60例,60~70 Gy者313例。Kaplan-Meier法计算总生存（OS）率、无进展生存（PFS）率,预后影响行Logrank单因素分析和Cox法多因素分析。结果 全组l、3、5年OS率和PFS率分别为69.4%、33.7%、22.9%和63.8%、32.8%、22.4%,中位OS和PFS分别为22.7个月（95%CI 18.6~25.4个月）和19.2个月（95%CI 16.7~21.3个月）。单因素分析显示,患者年龄、性别、肿瘤部位、不同三维技术、是否联合化疗、淋巴引流区是否预防照射、不同根治量对OS和PFS无影响（P>0.05）;T分期、N分期、TNM分期和GTV体积影响OS和PFS的因素（χ²=5.836~14.526,P<0.05）;多因素分析显示,N分期和GTV体积是影响OS和PFS的因素（χ²=5.345~12.216,P<0.05）。两个淋巴结区域转移患者的OS和PFS曲线均差于1个淋巴结区域转移者（χ²=4.467,4.169,P<0.05）。结论 食管癌患者采用三维技术放疗的长期疗效明显提高。N分期和肿瘤体积是影响患者预后的独立因素,淋巴结转移区域数与患者预后密切相关。     

Intra-abdominal mass with empty scrotum in adult male revealed as testicular seminoma: A case report

During fatal development, the testes grow in the abdomen and descend into the scrotal sac. It can be stopped at any point along its path (cryptorchidism) or migrate to an atypical side (ectopic testis).A 47-year-old man from Somalia''s lower Shabelle region was presented to the urology OPD, He had a history of non-tender abdominal mass for the previous four months, An examination revealed a mass in his abdomen that was firm, non-tender, and immobile, an abdominal ultrasound and a contrast enhanced CT abdomen showed a 15-cm heterogeneous bean-shaped mass above the bladder.After patient counseling and informed written consent, a laparotomy was done to remove the tumor. A seminoma of the undescended testis was identified during a histological examination.An intra-abdominal mass with empty scrotum should raise concerns about an intra-abdominal testicular tumor. To prevent/early discover these types of tumors, cryptorchidism should be treated at a young age, particularly before to the first year.     

The results of radiation therapy of patients with pure seminoma of the testis

Between 1967 and 1985, 75 patients with pure seminoma of the testis were treated with radiation therapy for periaortic and ipsilateral iliac areas following orchiectomy at the Department of Radiology, Osaka University Hospital. All patients except three were followed at least 2 years. Concerning patients who received 28-30 Gy, all of 48 patients with N0 disease were controlled and alive 2 to 20 years after radiation therapy. All of four patients with N1 disease were controlled and alive 6 to 16 years after radiation therapy. Six of 7 patients with N2 disease were controlled and alive 6 to 19 years after radiation therapy but one patient with T1N2 disease who received 30 Gy to periaortic and ipsilateral iliac areas had recurrence in a paraaortic lymph node 11 months after radiation therapy. As for patients with N3 disease two patients were controlled after 38 Gy and 48 Gy, respectively. No complication was observed after radiation therapy. No sterility seemed to be induced by irradiation to periaortic and ipsilateral iliac areas. It may be concluded that dose of 30 Gy to periaortic and ipsilateral iliac areas is recommended for patients with N0 disease. However, for patients with N1 or N2 disease higher dose of 35 Gy or more is recommended.