Clinical characteristics and survival outcomes of elderly patients with de novo metastatic germ cell tumors.

OBJECTIVES: To determine the outcomes for elderly patients with de novo metastatic germ cell tumors and the influence of patient age on adherence to standard chemotherapy. METHODS: A total of 150 patients who were initially diagnosed with metastatic germ cell tumors and treated at our institution between 2007 and 2021 were included. Patients were classified according to three age groups: aged <40, 40-49, and ≥50 years. Clinicopathological features, adherence to standard first-line chemotherapy, overall survival, and disease-free survival were compared between these groups. We also analyzed the outcomes of patients who received low-intensity induction chemotherapy due to adverse events and/or comorbidities. RESULTS: There was no significant difference in any of the survival outcomes and in the rate of adherence to standard first-line chemotherapy between the three age groups, although elderly patients with intermediate/poor prognosis group tended to receive less-intense chemotherapies. The rate of febrile neutropenia as a chemotherapy-related adverse event was significantly higher in patients aged ≥50 years. No statistical significance in survival outcomes was detected between the group of patients who received relatively low-intensity induction chemotherapy and those who received adequately intensive planned chemotherapy. CONCLUSIONS: The adherence rate of standard fist-line chemotherapy of elderly patients is almost comparable to that of younger patients, although some adverse events should be carefully managed. Even elderly patients with metastatic germ cell tumors can aim for equivalently good survival outcome like younger populations, with effort to adhere to standard chemotherapy.

Significant reduction in burden of metastatic disease by intermittent docetaxel therapy in a patient with castration-resistant prostate cancer.

Intermittent docetaxel therapy (IDT) is rarely used nowadays as a treatment option for men with metastatic castration-resistant prostate cancer (mCRPC) because of the widespread availability of androgen receptor axis-targeted therapy, which is less toxic. Therefore, there is limited information available on whether IDT has a clinical benefit in the treatment of men with mCRPC. This report describes the case of a 66-year-old man with a diagnosis of cT2N1M0 prostate cancer who underwent neoadjuvant combined androgen blockade and whole-pelvis radiation therapy. However, the tumor had progressed to mCRPC with metastasis to the bladder and a left pelvic lymph node within 2 years. Docetaxel had been administered as first-line chemotherapy, and the patient achieved a complete response in terms of the bladder metastasis. Docetaxel was stopped after 15 cycles. When a durable response had been maintained for more than 2 years, during which only androgen deprivation therapy was administered, the patient was switched to observation only. However, his prostate-specific antigen level gradually increased. Abiraterone was started as second-line therapy, during which there was a rapid increase in the PSA level. Computed tomography revealed further enlargement of the left pelvic lymph node, bladder metastasis, metastasis to the left common iliac lymph nodes, and several disseminated nodules around the bladder. Docetaxel was reintroduced as IDT for third-line therapy, and a complete response was achieved for all metastases, with the exception of the metastasis in the left pelvic lymph node. Thus far, the patient has survived for more than 7 years after starting docetaxel as first-line therapy for mCRPC. IDT is potentially useful in a subgroup of patients with mCRPC and could achieve long-term survival. Comprehensive genomic profiling may help physicians to select patients with mCRPC who are more likely to benefit from docetaxel than other systemic therapy.

Efficacy and safety of pembrolizumab for older patients with chemoresistant urothelial carcinoma assessed using propensity score matching.

BACKGROUND: We used real-world and large-scale data to assess the clinical efficacy and safety of pembrolizumab in older patients with advanced urothelial carcinoma (UC). METHODS: A total of 608 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. All patients were histologically diagnosed with pure UC. Using propensity score matching (PSM) (ECOG performance status, site of metastasis, hemoglobin level and neutrophil-to-lymphocyte ratio, 1:1 matching), the overall survival (OS) and adverse events (AEs) of patients <75 and ≥75 years old were compared. RESULTS: The median follow-up (IQR) period was 16.1 (9.9-20.5) months. After PSM, there were 215 patients each in the aged <75 years and aged ≥75-year-old groups. The median OS of all patients was estimated to be 10.4 months (95% confidence interval [CI] = 8.8-12.1). After PSM, the median OS was 7.8 months (95% CI = 5.2-10.4) in the <75-year-old group and 10.4 months (95% CI = 7.3-13.5) in the ≥75-year-old group (P = 0.186). Any-grade AEs were more frequently reported in the ≥75-year-old group in comparison to the age <75-year-old group (55.3% vs. 41.9%, P = 0.007), whereas there was no significant difference between the two groups in the incidence of grade ≥3 AEs (10.2% vs. 12.6%, P = 0.544). The objective response rate, defined as complete remission or a partial response, was 22.8% in the <75-year-old group and 25.1% in the ≥75-year-old group (P = 0.651). CONCLUSIONS: The present study demonstrates that age does not affect the efficacy and safety of pembrolizumab treatment for advanced chemoresistant UC. Pembrolizumab treatment should not be avoided based on chronological age; however, close monitoring for the development of treatment-related AE should be considered for older patients.

Pre-pembrolizumab neutrophil-to-lymphocyte ratio (NLR) predicts the efficacy of second-line pembrolizumab treatment in urothelial cancer regardless of the pre-chemo NLR.

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients.

[A Case of Calyceal Diverticula with Stones Treated by Ureteroscopic Management].

Most patients with calyceal diverticula stones are asymptomatic, but some patients experience fever and low back pain. Here we report a case of calyceal diverticula stones treated by ureteroscopic management. A 41-year-old woman with backache visited a local doctor. She was diagnosed with a urinary tract infection, and prescribed an antibiotic. Her symptoms began to improve, but the ultrasonography showed she had a left renal cystic lesion, so she visited our hospital. Abdominal contrast-enhanced computed tomography (CT) showing in-flow of a contrast agent into the left renal calyceal diverticula located stones in the upper pole. We performed ureteroscopic management of the calyceal diverticula stones in two stages. First, we expanded the neck of the calyceal diverticula by indwelling the ureteral stent at the calyceal diverticula. Then, using a ureteral dilator, we expanded the neck of the calyceal diverticula further and removed the stones in the calyceal diverticula. Treatment with ureteroscopic management was possible due to the location of the calyceal diverticula stones and the success rate was increased by performing the treatment in two stages.

[Initial Clinical Experience of Nivolumab for Metastatic Renal Cell Carcinoma].

Nivolumab was approved as a new agent for advanced renal cell carcinoma (RCC) in Japan on September 2016. Nivolumab is an immune checkpoint inhibitor that activates the cytotoxic immune response and has exerted antitumor effects in a mechanism different from other available molecular targeted agents. Therefore, its response pattern, efficacy and adverse events are different from those of the molecular targeted agents for RCC. Here, we report our initial clinical experience with nivolumab. From December 2016 to September 2017, we applied nivolumab to 7 patients with metastatic RCC. The most common metastatic site was the lungs, followed by lymph nodes, bones and brain. According to the immune-related response criteria, the efficacy was stable disease in 2 patients and progressive disease in 5 patients. In 5 cases with multiple metastases, responses differed with the site of metastasis. The response was best in lung metastasis and worst in brain metastasis. Six cases had minor adverse events. In two cases, we discontinued administration of nivolumab temporarily. The patients recovered completely and we considered nivolumab effective and safe for treatment of metastatic RCC.

Resonant and nonresonant multiphoton ionization processes in the mass spectrometry of explosives.

Multiphoton ionization processes were studied for three types of explosives using a line-tunable ultraviolet femtosecond laser. When peroxides such as triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD) were ionized through a nonresonant two-photon process, a molecular ion was dominantly observed by reducing the excess energy remaining in the ion. However, an aromatic nitro compound such as 2,4,6-trinitrotoluene (TNT) produced large signals arising from molecular and fragment ions by resonant two-photon ionization. In addition, only fragment ions were produced from a nonaromatic nitro compound such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), even when a resonant two-photon ionization process was employed, suggesting that a further reduction in excess energy would be necessary if a molecular ion were to be observed.