HER2-positive status is associated with increased risk of central nervous system (CNS) metastases in breast cancer patients. Leptomeningeal carcinomatosis (LMC) represents a rare but disastrous manifestation of metastatic breast cancer (MBC) with limited treatment options and poor prognosis. Several case reports of intrathecal (i.t.) trastuzumab in the treatment of LCM were published so far. Usually, i.t. trastuzumab was administered in monotherapy or in combination with metothrexate. Herein, we report for the first time two patients with metastatic breast cancer and leptomeningeal carcinomatosis treated by intrathecal methotrexate (15 mg total dose) and cytarabine (24 mg total dose) with escalating dose of trastuzumab. We observed that up to 100 mg of trastuzumab can be safely administered intratecally with i.t. metothrexate and cytarabine. Both patients achieved good control of leptomeningeal disease for 13.5 and 6 months without significant toxicity. We suggest that i.t. trastuzumab with cytarabine and metothrexate is associated with promising benefit and warrant further investigation.

Background: Treatment for cancer may lead to development of cognitive difficulties in cancer survivors. This study aimed to evaluate long-term cognitive functioning (CogF) in germ-cell tumor (GCT) survivors. Subjects, Materials, and Methods: GCT survivors (n = 155) from the National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function at a median of 10 years of follow-up (range: 5–32). The study group consisted of survivors receiving a cisplatin-based chemotherapy, radiotherapy to the retroperitoneal lymph nodes, or both, whereas the control group included survivors treated with orchiectomy only. Results: Of the total survivors, 138 received treatment beyond orchiectomy and 17 controls had orchiectomy alone. Any treatment resulted in significantly greater cognitive difficulties on the overall cognitive function score. Treatment with radiotherapy was associated with cognitive declines in overall cognitive functioning and in subscales for perceived cognitive impairment and cognitive impairment perceived by others (both p < .05). The burden of chemotherapy plus radiotherapy or radiotherapy versus controls resulted in the impairment in all cognitive functioning domains (all p < .05). Overall long-term cognitive impairment was independent of age in the multivariable analysis. Conclusion: This prospective study shows that GCT survivors suffer from a long-term CogF impairment. These results may help guide clinicians’ decisions in treatment and follow-up of GCTs. Implications for Practice: In this study, long-term survivors of germ-cell tumors have reported cognitive impairment after curative treatment with radiotherapy and chemotherapy compared with controls who had treatment with orchiectomy only. These data provide an argument against the use of adjuvant radiotherapy for stage I seminoma. Unnecessary overtreatment with chemotherapy and additional radiotherapy after chemotherapy should be avoided.

Mitochondrial bioenergetics reprogramming is an essential response of cells to stress. Platelets, an accessible source of mitochondria, have a crucial role in cancer development; however, the platelet mitochondrial function has not been studied in urothelial carcinoma (UC) patients. A total of 15 patients with UC and 15 healthy controls were included in the study. Parameters of platelet mitochondrial respiration were evaluated using the high-resolution respirometry method, and the selected antioxidant levels were determined by HPLC. In addition, oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS) concentration in plasma. We demonstrated deficient platelet mitochondrial respiratory chain functions, oxidative phosphorylation (OXPHOS), and electron transfer (ET) capacity with complex I (CI)-linked substrates, and reduced the endogenous platelet coenzyme Q₁₀ (CoQ₁₀) concentration in UC patients. The activity of citrate synthase was decreased in UC patients vs. controls (p = 0.0191). γ-tocopherol, α-tocopherol in platelets, and β-carotene in plasma were significantly lower in UC patients (p = 0.0019; p = 0.02; p = 0.0387, respectively), whereas the plasma concentration of TBARS was increased (p = 0.0022) vs. controls. The changes in platelet mitochondrial bioenergetics are consistent with cell metabolism reprogramming in UC patients. We suppose that increased oxidative stress, decreased OXPHOS, and a reduced platelet endogenous CoQ₁₀ level can contribute to the reprogramming of platelet mitochondrial OXPHOS toward the activation of glycolysis. The impaired mitochondrial function can contribute to increased oxidative stress by triggering the reverse electron transport from the CoQ₁₀ cycle (Q-junction) to CI.