Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

2015 ◽  
Vol 33 (28) ◽  
pp. 3116-3123 ◽  
Author(s):  
Jakob Lauritsen ◽  
Maria G.G. Kier ◽  
Mette S. Mortensen ◽  
Mikkel Bandak ◽  
Ramneek Gupta ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Cell Cancer ◽  
Late Toxicity ◽  
Germ Cell Cancer ◽  
Line Treatment ◽  
Disease Information ◽  
Number Of Patients ◽  
Increased Risk ◽  
Disseminated Disease

Purpose A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment for disseminated disease. Methods From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse and death were identified and compared with the International Prognostic Factors Study Group (IPFSG) classification. Results In total, 268 patients received more than one line of treatment for disseminated GCC. Approximately half of patients (n = 136) died as a result of GCC. The 132 remaining patients, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal impairment (HR, 8.3; 95% CI, 3.0 to 23.2), neurologic disorders (HR, 6.3; 95% CI, 3.1 to 12.6), and death as a result of other causes (HR, 2.6; 95% CI, 1.6 to 4.2). In large part, the IPFSG classification was confirmed in our population; however, we could not confirm the primary site and the level of human chorionic gonadotropin as independent factors. We identified increasing age as a possible new prognostic factor for treatment failure after second-line treatment (HR, 1.2 per 10 years; 95% CI, 1.2 to 15). Conclusion Patients with GCC who survive after more than one line of treatment for disseminated disease have a highly increased risk of late toxicity and death as a result of causes other than GCC. Therefore, they should be candidates for life-long follow-up. The IPFSG classification was confirmed in this unselected population.

scholarly journals Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology

2019 ◽  
Vol 20 (20) ◽  
pp. 5017 ◽  
Author(s):  
Leendert H. J. Looijenga ◽  
Chia-Sui Kao ◽  
Muhammad T. Idrees
Keyword(s):  
Germ Cell ◽  
Y Chromosome ◽  
Association Studies ◽  
Cell Cancer ◽  
Disorders Of Sex Development ◽  
Germ Cell Cancer ◽  
Genome Wide Association Studies ◽  
Sex Development ◽  
Stage Of Development ◽  
Increased Risk

The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased risk is due to the presence of part of the Y chromosome, i.e., GonadoBlastoma on Y chromosome GBY region, as well as anatomical localization and degree of testicularization and maturation of the gonad. The latter specifically relates to the germ cells present being at risk when blocked in an embryonic stage of development. GGCC originates from either germ cell neoplasia in situ (testicular environment) or gonadoblastoma (ovarian-like environment). These precursors are characterized by presence of the markers OCT3/4 (POU5F1), SOX17, NANOG, as well as TSPY, and cKIT and its ligand KITLG. One of the aims is to stratify individuals with an increased risk based on other parameters than histological investigation of a gonadal biopsy. These might include evaluation of defined susceptibility alleles, as identified by Genome Wide Association Studies, and detailed evaluation of the molecular mechanism underlying the DSD in the individual patient, combined with DNA, mRNA, and microRNA profiling of liquid biopsies. This review will discuss the current opportunities as well as limitations of available knowledge in the context of predicting the risk of GGCC in individual patients.

scholarly journals Low RBM3 Protein Expression Correlates with Clinical Stage, Prognostic Classification and Increased Risk of Treatment Failure in Testicular Non-Seminomatous Germ Cell Cancer

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0121300 ◽  
Author(s):  
Sven-Erik Olofsson ◽  
Björn Nodin ◽  
Alexander Gaber ◽  
Jakob Eberhard ◽  
Mathias Uhlén ◽  
...  
Keyword(s):  
Protein Expression ◽  
Treatment Failure ◽  
Germ Cell ◽  
Clinical Stage ◽  
Cell Cancer ◽  
Germ Cell Cancer ◽  
Increased Risk ◽  
Risk Of Treatment

scholarly journals Randomized Phase III Study Comparing Paclitaxel–Bleomycin, Etoposide, and Cisplatin (BEP) to Standard BEP in Intermediate-Prognosis Germ-Cell Cancer: Intergroup Study EORTC 30983

2012 ◽  
Vol 30 (8) ◽  
pp. 792-799 ◽  
Author(s):  
Ronald de Wit ◽  
Iwona Skoneczna ◽  
Gedske Daugaard ◽  
Maria De Santis ◽  
August Garin ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Group Versus ◽  
Progression Free Survival ◽  
Germ Cell Cancer ◽  
Phase Iii ◽  
Rank Test ◽  
Primary Analysis ◽  
Open Label ◽  
Number Of Patients

Purpose To compare the efficacy of four cycles of paclitaxel–bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC). Patients and Methods Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m2 in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual. Results Accrual was from November 1998 to April 2009. A total of 169patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different. Conclusion T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant.

Nonseminomatous Germ Cell Cancer of the Testis: Reducing Treatment-Related Morbidity in Patients With Disseminated Disease

1983 ◽  
Vol 129 (6) ◽  
pp. 1282-1282
Author(s):  
B.R. Paschal ◽  
H.B. Muss ◽  
F. Richards ◽  
M.R. Cooper ◽  
D.R. White ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Cancer ◽  
Disseminated Disease

Long-term effects on renal function and blood pressure of treatment with cisplatin, vinblastine, and bleomycin in patients with germ cell cancer.

1988 ◽  
Vol 6 (11) ◽  
pp. 1728-1731 ◽  
Author(s):  
S W Hansen ◽  
S Groth ◽  
G Daugaard ◽  
N Rossing ◽  
M Rørth
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Cancer ◽  
Long Term Effects ◽  
Increased Risk ◽  
The Mean

Long-term effects of cisplatin on renal function were investigated in 34 patients with germ cell cancer observed for a median of 65 months (range, 43 to 97 months). All patients achieved a complete remission after treatment with cisplatin (median dose 583 mg/m2), vinblastine, and bleomycin. None of the patients relapsed during follow-up. During treatment the glomerular filtration rate (GFR) decreased by 18% (P less than .05). During follow-up kidney function recovered in ten patients and partly improved in eight patients. Changes in plasma creatinine did not consistently correspond to alterations in GFR. The mean increase in systolic blood pressure during follow-up did not differ from the increase seen in a group of age-matched healthy men. The mean increase in diastolic pressure, however, was significant (P less than .05), but was entirely due to hypertension observed in six patients. Renography of these patients was normal. We conclude that the decrease in GFR observed during treatment with cisplatin is partly reversible. Cisplatin-treated patients have an increased risk of developing hypertension years after treatment.

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