Dose-Dependent Effect of Platinum-Based Chemotherapy on the Risk of Metachronous Contralateral Testicular Cancer

PURPOSE Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk. PATIENTS AND METHODS The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models. RESULTS CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HRper cycle, 0.74; 95% CI, 0.64 to 0.85). CONCLUSION Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk.

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Incidence and risk factors for contralateral testicular tumor.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.419 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 419-419

Author(s):

Joost Marijn Blok ◽

Harmke J. Groot ◽

Eline H. Huele ◽

Ronald De Wit ◽

Jourik A. Gietema ◽

...

Keyword(s):

General Population ◽

Germ Cell ◽

Germ Cell Tumor ◽

Cumulative Incidence ◽

Cox Model ◽

Testicular Tumor ◽

Cell Tumor ◽

Entire Cohort ◽

Platinum Based Chemotherapy ◽

Increased Risk

419 Background: Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a metachronous contralateral testicular tumor (CLTT). It is unclear whether the histology of the primary tumor and treatment with platinum-based chemotherapy are associated with the risk of CLTT. The primary aim of this study was to analyze the association between number of chemotherapy cycles and risk of CLTT. Methods: We evaluated the incidence of metachronous CLTT (≥2 months after diagnosis of primary TGCT) in a nationwide cohort consisting of patients diagnosed with TGCT between 1989 and 2007. Standardized incidence ratios (SIRs) were computed to compare CLTT incidence with TGCT in the general population and the cumulative incidence of CLTT was estimated. We analyzed the association between treatment with chemotherapy and risk of CLTT in a multivariate Cox-model. Results: The entire cohort consisted of 4,755 patients (seminoma: n=2,612; 54.9%, nonseminomatous germ cell tumor [NSGCT]: n=2,143; 45.1%). The median age at diagnosis was 33 years (IQR 26-40). A total of 1,047 patients (22.0%) were treated with platinum-based chemotherapy for their primary TGCT (seminoma: n=189, NSGCT: n=858). Median follow-up was 17.0 years (IQR 12.7-22.0). A CLTT was diagnosed in 136 patients. The median interval to CLTT diagnosis was 6.1 years (range 0.8-19.7). The overall 20-year cumulative incidence was 3.4% (95% CI 2.8-4.0) and was higher after seminoma (4.0%; 95% CI 3.3-4.9), compared to NSGCT (2.6%; 95% CI 1.9-3.4). The SIRs were for seminoma: 22.1 (95% CI 17.8-27.1), for NSGCT: 8.6 (95% CI 6.3-11.6) and for the entire cohort: 14.6 (95% CI 12.2-17.2). In multivariate analysis, the risk of developing a CLTT decreased with age (HR 0.93; 95% CI 0.90-0.96), was lower after NSGCT (HR 0.58; 95% CI 0.35-0.96), and decreased with every additional cycle of chemotherapy (HR 0.74; 0.64-0.85). This corresponds to a 26% lower risk of CLTT per extra chemotherapy cycle. Conclusions: TGCT patients have an almost 15 times higher risk of developing a CLTT, compared to the general population. The risk is 2 times higher after a seminoma, compared to NSGCT, and decreases with every additional cycle of chemotherapy. Especially in high risk patients, lifelong self-examination is advised.

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Association of testicular germ cell tumor with polymorphisms in estrogen receptor and steroid metabolism genes

Endocrine Related Cancer ◽

10.1677/erc-09-0176 ◽

2010 ◽

Vol 17 (1) ◽

pp. 17-25 ◽

Cited By ~ 40

Author(s):

Alberto Ferlin ◽

Francesco Ganz ◽

Manuel Pengo ◽

Riccardo Selice ◽

Anna Chiara Frigo ◽

...

Keyword(s):

Estrogen Receptor ◽

Germ Cell ◽

Germ Cell Tumor ◽

Cancer Susceptibility ◽

Current Knowledge ◽

Testicular Germ Cell Tumor ◽

Cell Tumor ◽

Hormone Metabolism ◽

Testicular Germ Cell ◽

Increased Risk

It is generally assumed that the development of testicular germ cell tumor (TGCT) is under endocrine control. In particular, unbalanced androgen/estrogen levels and/or activity are believed to represent the key events for TGCT development and progression. Furthermore, recent evidence has suggested a strong genetic component for TGCT. In this study, we analyzed whether a genetic variation in estrogen receptor (ESR) genes and steroid hormone metabolism genes is associated with TGCT. We genotyped for 17 polymorphic markers in 11 genes in 234 TGCT cases and 218 controls: ESR (ESR1 and ESR2); CYP19A1 (aromatase); 17β-hydroxysteroid dehydrogenase types 1 and 4 (HSD17B1 and HSD17B4) dehydrogenases that convert potent androgens and estrogens to weak hormones; cytochrome P450 hydroxylating enzymes CYP1A1, CYP1A2, and CYP1B1; and the metabolic enzymes COMT, SULT1A1, and SULT1E1. We observed a significant association of rs11205 in HSD17B4 with TGCT. TGCT risk was increased twofold per copy of the minor A allele at this locus (odds ratios (OR)=2.273, 95% confidence interval (CI)=1.737–2.973). Homozygous carriage of the minor A allele was associated with an over fourfold increased risk of TGCT (OR=4.561, 95% CI=2.615–7.955) compared with homozygous carriage of the major G allele. The risk was increased both for seminoma (OR=5.327, 95% CI=2.857–9.931) and for nonseminoma (OR=3.222, 95% CI=1.471–7.059). We found for the first time an association of polymorphisms in HSD17B4 gene with TGCT. Our findings expand the current knowledge on the role of genetic contribution in testicular cancer susceptibility, and support the hypothesis that variations in hormone metabolism genes might change the hormonal environment implicated in testicular carcinogenesis.

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Increased risk of testis failure in testicular germ cell tumor survivors undergoing radiotherapy

Oncotarget ◽

10.18632/oncotarget.23081 ◽

2017 ◽

Vol 9 (3) ◽

pp. 3060-3068 ◽

Cited By ~ 4

Author(s):

Marco Ghezzi ◽

Luca De Toni ◽

Pierfrancesco Palego ◽

Massimo Menegazzo ◽

Elisa Faggian ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Testicular Germ Cell Tumor ◽

Cell Tumor ◽

Testicular Germ Cell ◽

Increased Risk

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Abstract 2644: No evidence for increased risk of cancers other than testicular cancer among first-degree relatives of testicular germ cell tumor (TGCT) patients from multiple-case TGCT families

10.1158/1538-7445.am2012-2644 ◽

2012 ◽

Author(s):

Mary L. McMaster ◽

Ketil R. Heimdal ◽

Mark H. Greene

Keyword(s):

Testicular Cancer ◽

Germ Cell ◽

Germ Cell Tumor ◽

Testicular Germ Cell Tumor ◽

Cell Tumor ◽

Testicular Germ Cell ◽

First Degree Relatives ◽

Increased Risk ◽

Multiple Case

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Diagnostic radiation and testicular germ cell tumor risk.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.556 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 556-556

Author(s):

Kevin Thomas Nead ◽

Nandita Mitra ◽

Benita Weathers ◽

Louisa T Pyle ◽

Katherine L. Nathanson ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Testicular Germ Cell Tumor ◽

Cell Tumor ◽

The Body ◽

Testicular Germ Cell ◽

X Ray ◽

Increased Risk ◽

Diagnostic Radiation ◽

History Of

556 Background: Both incidence of testicular germ cell tumor (TGCT) and use of diagnostic radiation have increased in recent decades. In a quarter of diagnostic scans in children, direct and indirect radiation dose to the testes exceeds 20 mSv, which surpasses thresholds associated with malignancy risk (~5 mSv). Here, we examine the association between exposure to diagnostic radiation and TGCT risk in a case-control study. Methods: Cases were enrolled in a hybrid hospital- and population-based setting and controls were recruited from the community. Participants reported on exposures to x-ray/CT below the waist and lower GI series, and we derived a combined variable for any exposure. After imputation to infer missing data, we compared baseline characteristics and used multivariable logistic regression adjusting for age and race to determine the risk of developing TGCT according to number of exposures and age at first exposure. Results: As expected, cases (n = 1088) were more likely than controls (n = 1458) to be white, have a family history of TGCT, and have a history of cryptorchidism (p < 0.05). There was an increased risk of TGCT with a greater number of exposures for both x-ray/CT (ptrend= 0.002) and the combined diagnostic radiation variable (ptrend< 0.001). Compared to those without any exposure, risk was greatest among those reporting ≥6 exposures for x-ray or CT (OR, 9.6; 95% CI, 4.6-19.9; p < 0.001) and the combined variable (OR, 5.8; 95% CI, 3.2-10.4; p < 0.001), after adjusting for age at first exposure. Early first exposure before eleven years of age increased risk of TGCT for x-ray/CT (OR, 2.36; 95% CI, 1.17-4.77) and combined radiation exposure (OR, 1.96; 95% CI, 1.05-3.67) compared to later first exposure after seventeen years of age, adjusting for total exposures. Analyses limited to observed data only yielded similar results. Conclusions: Exposure to diagnostic radiation below the waist, particularly among younger individuals, may increase TGCT risk. These results should be validated. As the testes are present outside the body and rarely examined using diagnostic radiation, a unique opportunity for shielding exists. Efforts to reduce testicular dose and optimize shielding practices should be prioritized.

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Faculty Opinions recommendation of Anxiety and depression in long-term testicular germ cell tumor survivors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732149433.793539484 ◽

2017 ◽

Author(s):

David Spiegel

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Testicular Germ Cell Tumor ◽

Cell Tumor ◽

Anxiety And Depression ◽

Testicular Germ Cell

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GCT-06. DIAGNOSIS OF A RARE CASE OF RECURRENT GERM CELL TUMOR BY CSF PLACENTAL ALKALINE PHOSPHATASE PRESENTING WITH DIFFUSE INTRAAXIAL ABNORMALITY IN THE LOWER BRAINSTEM

Neuro-Oncology ◽

10.1093/neuonc/noaa222.228 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii329-iii329

Author(s):

Hiroki Yamada ◽

Tomohiro Abiko ◽

Hirokazu Fujiwara ◽

Kazunari Yoshida ◽

Hikaru Sasaki

Keyword(s):

Alkaline Phosphatase ◽

Germ Cell ◽

Germ Cell Tumor ◽

Rare Case ◽

Cervical Spinal Cord ◽

Germ Cell Tumors ◽

Cell Tumor ◽

Placental Alkaline Phosphatase ◽

Steroid Pulse ◽

Platinum Based Chemotherapy

Abstract INTRODUCTION Germ cell tumors in the central nervous system (CNS) typically arise either at suprasellar and/or pineal region, and occasionally at basal ganglia. We report a case of diagnostically challenging, recurrent germ cell tumor presented with diffuse intraaxial abnormality in and across the lower brainstem, which was diagnosed by the elevated placental alkaline phosphatase (PLAP) level in cerebrospinal fluid (CSF). CASE DESCRIPTION: A 28-year-old man had been treated by chemoradiotherapy at the previous hospital for bifocal suprasellar and pineal lesions with the provisional diagnosis of germinoma without histological confirmation. Three years later, he presented with progressive weakness of bilateral extremities for weeks. Magnetic resonance imaging showed a diffuse, bilaterally symmetric high intensity lesion on T2-weighted image with slight contrast enhancement across the ventral side of the medulla oblongata to the upper cervical spinal cord. Serum and CSF hCG, hCG-β, and AFP were all negative. Since the image findings were atypical for recurrent germ cell tumor, some kind of myelitis was initially suspected. Therefore, steroid pulse therapy was administered. However, the patient’s symptom was still gradually progressing. Then, the CSF PLAP turned out to be positive, indicating the recurrence of germinoma. Accordingly, platinum-based chemotherapy was administered, and the imaging findings, patient’s symptoms, and CSF PLAP began to improve. The patient is to be treated with radiotherapy following chemotherapy. CONCLUSION We report a rare case of CNS germ cell tumor that presented with diffuse intraaxial lesion in the lower brainstem in which examination of CSF PLAP was extremely useful.

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