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Purpose: Visual impairment represents an infrequent form of cisplatin-induced neurotoxicity; however, visual deterioration has been reported in several studies. To evaluate potential morphological and functional retinal alterations in patients with germ cell cancer (GCC) treated with cisplatin-based chemotherapy (CBC). Methods: Multi-disciplinary and multi-institutional study design. Examination of 28 eyes of 14 male GCC patients, who had received at least one cycle of CBC. A matched control group of healthy, untreated patients were included in this study. Subjects underwent a retinal nerve fiber thickness (RNFL) measurement, color vision, visual acuity testing, full-field electroretinograms (ff-ERG). To assess a correlation between cumulative cisplatin dose and measured RNFL and ff-ERG Pearson correlation coefficient analysis was performed. Results: Both study groups (CBC recipients vs. healthy controls) consisted each of 14 participants with a median patient age of 30 years (interquartile range (IQR) 26-37 years). Tumor histology was seminoma in 6 of 14 patients (43%), and non-seminomatous GCC in 8 of 14 patients (57%). Median cumulative cisplatin dosis at examination was 627 mg/m (IQR 413-1013 mg/m). Morphological assessment revealed reduced RNFL in 11 of 14 patients (78.6%). Reduction in RNFL was significantly correlated to the cumulative CBC dose received (rho = + 0.70; p = 0.004). ff-ERG showed significant differences between CBC recipients and the control group in 2 of 5 tested categories (all p values <0.001). Conclusion: This study represents first evidence of chronic subclinical retinal toxicity due to cisplatin-based chemotherapy in patients with GCC. The reduction of RNFL might become clinically relevant in upcoming age-related chronic degenerative disorders such as glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively analyze clinical characteristics, prognostic factors, and optimal treatment of patients with bone metastases (BM) of germ cell tumors (GCT) at first relapse. Methods: One hundred and four GCT patients with BM were identified from the IPFSG database containing 1,594 patients at first relapse. Within this database, all patients experienced unequivocal relapse/progression after cisplatin-based chemotherapy and had received either conventional (CD-CTX) or high-dose chemotherapy (HD-CTX) as first salvage treatment. Results: At relapse, eight patients (8 %) had BM only, concomitant relapse with lung, brain, liver and/or nodal metastases were present in 40 (39 %), 6 (6 %), 27 (26 %), and 69 (66 %) pts, respectively. Patients clustered over all IPFSG subgroups, and the IPFSG score could be confirmed. Salvage treatment was CD-CTX in 35 and HD-CTX in 69 patients. Overall response (CR, PR) rate to salvage chemotherapy was 81 % (HD-CTX) versus 43 % (CD-CTX; p < 0.001). Median follow-up was 14 months (mos; range 1-161). Both, median PFS and OS, were higher after HD-CTX compared to CD-CTX [PFS 9 (95 % CI 6-12) vs. 5 (3-7) mos ( p < 0.01); OS 18 (12-24) vs. 13 (8-18) mos ( p = 0.078)]. Conclusions: GCT patients relapsing with BM have a dismal outcome. Retrospectively, first salvage HD-CTX seems to improve treatment response and outcome. Further evaluation of characteristics and treatment of GCT patients with BM is warranted. [ABSTRACT FROM AUTHOR]

Purpose: We analyzed prognostic categories at first relapse according to the International Prognostic Factors Study Group (IPFSG) criteria as well as the efficacy of salvage treatment. Methods: 143 patients with relapsed or refractory germ cell cancer undergoing first salvage treatment with conventional-dose (CD-CX, n = 48) or high-dose chemotherapy with autologous stem cell support (HD-CX, n = 95) contributed by nine centers were retrospectively analyzed. Results: Prognostic subgroups according to IPFSG criteria were: very low risk 13/143, low risk 36/143, intermediate risk 66/143, high risk 22/143, and very high risk 6/143 patients. The IPFSG categories significantly correlated with overall survival (OS) ( p = 0.025) after 1st salvage treatment. After a median follow-up of 19 months, 55 % of all patients had relapsed and 33 % had died. For the entire cohort, progression-free survival (PFS) rate after 2 years was 43 %, and OS rate after 5 years was 52 %. Compared to the HD-CX group, vital carcinoma was found more often in secondarily resected lesions following CD-CX (22/29 vs. 22/45; p = 0.021). Second relapse rate was higher with 75 versus 44 %, resulting in a shorter median PFS with 8 versus 42 months ( p < 0.001), but this did not translate into different OS ( p = 0.931). At subsequent relapses, 26/36 patients received HD-CX as ≥2nd-salvage treatment. Conclusion: This analysis confirms the prognostic value of the IPFSG prognostic score. HD-CX seemed superior to CD-CX as first salvage treatment with respect to PFS in this retrospective analysis. [ABSTRACT FROM AUTHOR]

Purpose: Little data exist on characteristics, treatment, and outcome of patients with bone metastases from germ cell cancer. Methods: A total of 434 patients with poor prognosis germ cell cancer, who underwent primary high-dose chemotherapy (HD-CTX) within two phase II trials, were retrospectively analyzed. Results: 40 patients (9%) presented with primary bone metastases. Bone metastases were significantly more frequently observed in patients with primary mediastinal tumors, yolk sac tumor histology, and synchronous liver metastases. Overall response rate to HD-CTX was 85%. 20% of patients underwent consolidating radiotherapy, and 10% had resection of bone metastases revealing necrosis in all cases. Progression-free survival rate after primary treatment was 63% and, including salvage treatment after first relapse, overall long-term survival rate was 75%. Four patients (0.9%) relapsed with isolated bone metastases, all with bone metastases at primary diagnosis. None had previously received surgery or radiotherapy and all died within 1 year. 10 patients with primary bone metastases showed recurrences at other localizations. No patient relapsed with bone plus other metastases or with de novo bone metastases. Conclusions: Bone metastases were associated with a primary mediastinal nonseminoma, yolk sac histology, and liver metastases at first diagnosis. In this cohort of patients receiving HD-CTX as first-line treatment, 63% achieved long-term progression-free survival. Skeletal relapses were rare, but showed dismal outcome. [ABSTRACT FROM AUTHOR]