Kiyoaki Nishihara

Personalized peptide vaccination as second-line treatment for metastatic upper tract urothelial carcinoma

This study investigated the applicability of personalized peptide vaccination (PPV) for patients with metastatic upper tract urothelial cancer (mUTUC) after failure of platinum‐based chemotherapy. In this single arm, open‐label, phase II clinical trial, patients with mUTUC received PPV at a single institution. Personalized peptide vaccination treatment used a maximum of four peptides chosen from 27 candidate peptides according to human leukocyte antigen types and peptide‐reactive IgG titers, for six s.c. injections weekly as one cycle. The safety of PPV, as well as its influence on host immunity and effect on overall survival were assessed. Forty‐eight patients were enrolled in this study. Personalized peptide vaccinations were well tolerated without severe adverse events. Median survival time was 7.3 months (95% confidence interval [CI], 5.3–13.1) with 13.0 months for patients receiving combined salvage chemotherapy (95% CI, 5.7–17.5) and 4.5 months for patients receiving PPV alone (95% CI, 1.7–10.1) (P = 0.080). Patients with positive CTL responses showed a significantly longer survival than patients with negative CTL responses (hazard ratio, 0.37; 95% CI, 0.16–0.85; P = 0.019). Multivariate Cox regression analysis showed that lower numbers of Bellmunt risk factors and lower levels of B‐cell activating factor were significantly associated with favorable overall survival for patients under PPV treatment. This study indicated that PPV for patients with mUTUC after failure of platinum‐based chemotherapy induced substantial peptide‐specific CTL responses without severe adverse events and has the potential to prolong survival when combined with salvage chemotherapy.

Demographics, management and treatment outcomes of benign and malignant retroperitoneal tumors in Japan

To show the demographics, type of treatment and clinical outcomes of patients with retroperitoneal tumors in Japan.

Comprehensive Health-Related Quality of Life is Influenced by Nocturia and Sleep Disturbance: Investigation Based on the SF-8

We investigated the influence of nocturia and sleep disturbance on health-related quality of life(HRQOL) using the Medical Outcomes Study 8-item Short Form Health Survey (SF-8) in patients with nocturia. We also assessed the effect of therapeutic intervention by means of an anticholinergic agent on the results of the SF-8. One hundred and eighty-four patients who voided at least once per night were surveyed using the SF-8, Overactive Bladder Symptom Score (OABSS), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). These parameters were also evaluated before and after 12 weeks of imidafenacin treatment in 51 patients with OAB accompanied by nocturia. The SF-8 physical component summary score (PCS) showed a significant decrease as nighttime voiding frequency increased. The mental health component summary score was 47.1 and 47.6 (which were lower than the standard value of 50) in the group with a nighttime frequency of once and ≥3/night, respectively. The SF-8 PCS and 6 subscales were negatively associated with nighttime voiding frequency, while the PSQI global score was positively associated with it. Imidafenacin significantly improved the OABSS, PSQI, and ESS, as well as the SF-8 score. This is the first study using the SF-8 to show that nocturia and sleep disturbance have a major influence on comprehensive HRQOL and that the SF-8 can be used to monitor HRQOL in OAB patients receiving treatment for nocturia.

Relationship between sexual function and prostate-specific antigen bounce after iodine-125 permanent implant brachytherapy for localized prostate cancer

To analyze clinical and dosimetric factors involved in prostate‐specific antigen bounce in patients who underwent permanent implant brachytherapy for localized prostate cancer, and to study the relationships among prostate‐specific antigen bounce, age and sexual function.

Improvement in urinary retention due to recurrent anastomotic prostate cancer treated with various therapies by intra-arterial infusion of cisplatin and ifosfamide

Although many treatments have been applied to treat hormone-refractory prostate cancer (HRPC), therapeutic outcome is not altogether satisfactory. In the case of locally recurring HRPC, uncontrolled gross hematuria, dysuria, and scalding are often experienced. We report a patient who improved following intra-arterial infusion of cisplatin (CDDP) and ifosfamide (IFM) to treat urinary retention caused by locally recurring HRPC. After chemotherapy, cancer volume was remarkably reduced and symptoms improved.

Early primary renal tumor response predicts clinical outcome in patients with primary unresectable renal cell carcinoma with synchronous distant metastasis receiving molecularly targeted therapies

The aim of the present study was to investigate the prognostic factors for patients with primary unresectable renal cell carcinoma (RCC) with synchronous distant metastasis receiving molecularly targeted therapies. A total of 26 patients with primary unresectable RCC with synchronous distant metastasis underwent molecularly targeted therapies at the Kurume University Hospital (Kurume, Japan) between March 2008 and March 2016. Early primary renal tumor response was evaluated at 8-12 weeks after the introduction of molecularly targeted therapy and a 10% decrease in the diameter of primary renal tumor was used as the cut-off value. The median overall survival from the initiation of first-line molecularly targeted therapy was 18.3 months. Univariate analyses for various factors identified early primary renal tumor response (P=0.0004) and best response to first-line treatment (P=0.0002) as prognostic variables. Multivariate analyses also identified early primary renal tumor response (P=0.0099) and best response to first-line treatment (P=0.0054) as independent prognostic factors. A comparison of clinical characteristics between the group with ≥10% shrinkage and the group with disease progression or <10% shrinkage revealed that the number of metastatic sites and pretreatment monocyte-to-lymphocyte ratio tended to be predictive factors for primary renal tumor response. These results suggest that early primary renal tumor shrinkage is highly variable for patients with primary unresectable RCC with synchronous distant metastasis receiving molecularly targeted therapies.

Long-term response of over ten years with sorafenib monotherapy in metastatic renal cell carcinoma: a case report.

BackgroundMolecular targeted therapies have dramatically improved the prognosis of metastatic renal cell carcinoma. However, patients in whom the treatment could initially be effective will experience disease progression later.Case presentationA 74-year-old Japanese man who was diagnosed with renal cell carcinoma with no evidence of metastasis presented to our hospital. He initially underwent radical nephrectomy, and subsequently the disease metastasized to the lung. Sorafenib was started for the lung metastases 1 year after the operation. The dose of sorafenib was reduced and temporarily discontinued because adverse events, including fatigue and cardiac infarction, occurred. The patient has continued sorafenib monotherapy for over 10 years without disease progression and severe adverse events.ConclusionsWe present a rare case of a patient with metastatic renal cell carcinoma who has survived for over 10 years while receiving sorafenib monotherapy.

Prognostic value of PD-1 and PD-L1 expression in patients with metastatic clear cell renal cell carcinoma

OBJECTIVE In renal cell carcinoma (RCC), several prognostic biomarkers have been identified and are under investigation. Several reports have shown that the expression of programmed death 1 (PD-1) and its ligand PD-L1 is associated with poor outcome for patients with RCC. The present study is aimed at evaluating the expression of PD-1 and PD-L1 and to investigate their clinical and prognostic significance in patients with clear cell RCC (CCRCC) having received molecular targeted therapies. In addition, we also evaluated the relationship between the expression of PD-1 and PD-L1 and intratumoral tumor infiltrating lymphocytes (TILs). METHODS A total of 33 patients with metastatic CCRCC who underwent surgery and received molecular targeted therapies from March 2008 to April 2016 were retrospectively reviewed and analyzed. Tissue specimens from the patients were analyzed for PD-1 and PD-L1 expression by immunohistochemistry. RESULTS The median patient age was 64 years old (range=53-78). The majority of patients were male (81.8%). All Memorial Sloan Kettering Cancer Center risk groups were represented among the patients with 39.4% with favorable-, 51.5% with intermediate- and 9.1% with poor-risk. The expression of PD-1 and PD-L1 was observed in 16 (48.5%) and 9 (27.3%) patients, respectively. The expression of PD-1 and PD-L1 was associated with a larger primary renal tumor size, higher nuclear grade and sarcomatoid feature. Kaplan-Meier analysis revealed that no significant difference in progression free survival of first line molecular targeted therapy was found for PD-1 (P=0.2396) and PD-L1 (P=0.5919) expression. However, PD-1 expression has a significant worse impact on overall survival (OS) (P=0.0385), while for PD-L1 expression only a trend is seen for OS (P=0.1542). The patients with PD-1 and PD-L1 expression showed higher infiltration of CD4 (P<0.0001 and P<0.0001, respectively), CD8 (P=0.0328 and P=0.0044, respectively) and FOXP3 (P<0.0001 and P=0.0033, respectively) positive TILs. CONCLUSION PD-1 and PD-L1 expression is significantly associated with adverse clinicopathological features in CCRCC. Furthermore, PD-1 expression could be one of the biomarkers suggesting poor outcome in patients with metastatic CCRCC receiving molecular targeted therapies.

Efficacy of Axitinib as Second-line Treatment in Locally Advanced and Metastatic Renal Cell Carcinoma

Aim: To investigate prognostic factors for patients with advanced renal cell carcinoma (RCC) treated with axitinib as second-line therapy. Patients and Methods: This study included 35 patients with RCC who received axitinib as second-line therapy after the failure of first-line tyrosine kinases inhibitor from November 2012 to March 2017. Results: In univariate analyses, the following factors were associated with poor prognosis: bone and extrapulmonary metastasis for progression-free survival; and prior nephrectomy, Memorial Sloan Kettering Cancer Center risk classification, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification of poor, extrapulmonary metastasis and early tumor response for overall survival. Multivariate analyses identified the following factors as independent poor prognostic effects: extrapulmonary metastasis for progression-free survival, and no prior nephrectomy, IMDC risk classification of poor and extrapulmonary metastasis for overall survival. Conclusion: Axitinib as second-line treatment is effective for patients with pulmonary metastasis alone of RCC, but not for those with extrapulmonary metastasis.

MP78-06 PHASE II STUDY OF PERSONALIZED PEPTIDE VACCINATION FOR METASTATIC UPPER TRACT UROTHELIAL CANCER PATIENTS REFRACTORY TO THE STANDARD CHEMOTHERAPY

Shinichi Yamashita*, Akihiro Ito, Koji Mitsuzuka, Masataka Aizawa, Naomasa Ioritani, Sendai, Japan; Shigeto Ishidoya, Sendai, Japan; Yoshihiro Ikeda, Osaki, Japan; Kenji Numahata, Yamagata, Japan; Kazuhiko Orikasa, Kesennuma, Japan; Tatsuo Tochigi, Natori, Japan; Fumihiko Soma, Hachinohe, Japan; Takashige Namima, Hideo Saito, Sendai, Japan; Makoto Sato, Rifu, Japan; Shinnosuke Katoh, Yuzawa, Japan; Shozo Ota, Sendai, Japan; Atsushi Kyan, Shirakawa, Japan; Atsushi Takeda, Ichinoseki, Japan; Yasuhiro Kaiho, Yoichi Arai, Sendai, Japan