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Cancer Statistics
Population in 2012: 126.4m
People newly diagnosed with cancer (excluding NMSC) / yr: 703,900
Age-standardised rate, incidence per 100,000 people/yr: 217.1
Risk of getting cancer before age 75:21.8%
People dying from cancer /yr: 378,600
Data from IARC GlobalCan (2012)
Japan: Cancer Organisations and Resources
Japan: Cancer Centres
Journals of Japanese Societies
Latest Research Publications related to Japan

Japan: Cancer Organisations and Resources (12 links)

Japan: Cancer Centres (6 links)

Journals of Japanese Societies (5 links)

See also: Oncology Journals

Latest Research Publications related to Japan

Yamasaki S, Nitta H, Kondo E, et al.
Effect of allogeneic hematopoietic cell transplantation for patients with T-prolymphocytic leukemia: a retrospective study from the Adult Lymphoma Working Group of the Japan Society for hematopoietic cell transplantation.
Ann Hematol. 2019; 98(9):2213-2220 [PubMed] Related Publications
Alemtuzumab is the treatment choice for patients with T-prolymphocytic leukemia (T-PLL). However, patients with T-PLL have a poor prognosis, and the option of allogeneic hematopoietic cell transplantation (HCT) remains controversial in these patients. This study aimed to analyze the outcomes of allogeneic HCT among patients with T-PLL to identify the potential clinical efficacy of allogeneic HCT. We retrospectively analyzed data from 20 patients with T-PLL, including five patients with complex chromosomal abnormalities at diagnosis who received an allogeneic HCT between 2000 and 2016. The median follow-up of survivors was 51 months in allogeneic HCT from human leukemia antigen (HLA)-matched donors. All five patients with complex chromosomal abnormalities died after allogeneic HCT. Our data suggest that allogeneic HCT from an HLA-matched donor can be considered for patients with T-PLL without complex chromosomal abnormalities. New treatment strategies of allogeneic HCT are required to improve the safety and efficacy of allografting in patients with T-PLL and complex chromosomal abnormalities. Potential approaches that identify patients with T-PLL and complex chromosomal abnormalities for allogeneic HCT with better disease control may allow identification of individuals who are suitable for allogeneic HCT.

Yasuoka S, Yuasa T, Nishimura N, et al.
Initial Experience of Pembrolizumab Therapy in Japanese Patients With Metastatic Urothelial Cancer.
Anticancer Res. 2019; 39(7):3887-3892 [PubMed] Related Publications
BACKGROUND/AIM: Pembrolizumab was approved as second-line treatment for patients with metastatic urothelial cancer (UC) in Japan. We performed a retrospective pilot study to assess the potency of pembrolizumab treatment in Japan.
PATIENTS AND METHODS: The medical records of 40 consecutive Japanese patients with metastatic UC who started pembrolizumab between January and October 2018 were reviewed and statistically analyzed to clarify the efficacy and safety of the drug.
RESULTS: The objective response rate, median progression-free survival period, and median overall survival period were 20.6%, 4.1 months and 10.0 months, respectively. Multivariate analysis indicated the presence of liver metastasis, worse performance status (≥2), and higher C-reactive protein as factors predictive of shorter OS.
CONCLUSION: We demonstrated for the first time, a comparable efficacy and safety profile of pembrolizumab for Japanese patients with metastatic UC, as in the KEYNOTE-045 study. The results indicate the features of pembrolizumab therapy in the current Japanese clinical practice.

Ishikura N, Usui Y, Ito H, et al.
Helicobacter pylori (HP) infection alone, but not HP-induced atrophic gastritis, increases the risk of gastric lymphoma: a case-control study in Japan.
Ann Hematol. 2019; 98(8):1981-1987 [PubMed] Related Publications
Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45-1.33), 0.65 (0.30-1.39), 1.03 (0.38-2.79), and 0.84 (0.22-3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30-3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00-3.86), 1.92 (0.74-4.95), and 5.80 (1.12-30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma.

Kobayashi T, Namitome R, Hirata YU, et al.
Serum Prognostic Factors of Androgen-deprivation Therapy Among Japanese Men With
Anticancer Res. 2019; 39(6):3191-3195 [PubMed] Related Publications
BACKGROUND/AIM: To date, several serum prognostic factors have been reported in metastatic prostate cancer. In this study, we examined the prognostic value of these serum markers in Japanese men.
PATIENTS AND METHODS: This study included 104 patients with metastatic prostate cancer who were treated with primary androgen-deprivation therapy from 2001 to 2013. Clinicopathological factors including several serum markers were investigated for association with progression-free (PFS) and overall (OS) survival.
RESULTS: During a median follow-up of 48.1 months, median PFS and OS were 24.0 months and 67.4 months, respectively. When adjusted by age, prostate-specific antigen at diagnosis, Gleason score, and clinical stage, serum lactate dehydrogenase value was significantly associated with PFS [hazard ratio (HR)=1.42, 95% confidence interval (CI)=1.15-1.74; p=0.0004] and OS (HR=1.46, 95% CI=1.13-1.82; p=0.0014), in addition to alkaline phosphatase value for OS (HR=1.04; 95% CI=1.00-1.07; p=0.015).
CONCLUSION: This study demonstrates the prognostic significance of alkaline phosphatase and lactate dehydrogenase values in Japanese men with de novo metastatic hormone-sensitive prostate cancer.

Ito T, Kanao K, Takahara K, et al.
Optimal Timing of Cabazitaxel Introduction for Japanese Patients With Metastatic Castration-resistant Prostate Cancer.
Anticancer Res. 2019; 39(6):3089-3094 [PubMed] Related Publications
BACKGROUND/AIM: Limited information is available to help physicians decide when to introduce cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) patients. The objective of this study was to assess the optimal timing of cabazitaxel introduction.
PATIENTS AND METHODS: The clinical outcomes of 66 mCRPC patients receiving cabazitaxel following failure of docetaxel were retrospectively analyzed.
RESULTS: Among the parameters possibly affecting the timing of cabazitaxel introduction, only an increased prostate-specific antigen (PSA) value from the diagnosis of CRPC had a significant impact on overall survival (OS) after the introduction of cabazitaxel. Furthermore, there was a significant correlation between the increased PSA value from the diagnosis of CRPC and the baseline PSA value at cabazitaxel introduction. Multivariate analysis showed that only the baseline PSA value at cabazitaxel introduction is an independent predictor of OS.
CONCLUSION: A comparatively low PSA value could be an alternative index suggesting the optimal timing for cabazitaxel introduction.

Mikoshiba T, Ozawa H, Saito S, et al.
Usefulness of Hematological Inflammatory Markers in Predicting Severe Side-effects from Induction Chemotherapy in Head and Neck Cancer Patients.
Anticancer Res. 2019; 39(6):3059-3065 [PubMed] Related Publications
BACKGROUND: Induction chemotherapy (IC) for head and neck cancer (HNC) often causes severe side-effects. However, it has still been challenging to predict the adverse events. The present study aimed to evaluate the role of hematological inflammatory markers in predicting severe side-effects caused by IC.
MATERIALS AND METHODS: A total of 54 HNC patients who underwent IC were enrolled. The association between severe side-effects and pre-treatment hematological inflammatory markers [the C-reactive protein (CRP) to albumin ratio (CAR), the modified Glasgow Prognostic Score (mGPS), the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR)] were evaluated.
RESULTS: In the univariate analysis, the incidence of whole severe side-effects (grade 4), febrile neutropenia (above grade 3), and hyponatremia (above grade 3) were significantly higher in the high CAR and high GPS groups. Multivariate analysis revealed that high CAR and mGPS were independent predictors of these side-effects.
CONCLUSION: CAR and mGPS were significant predictors of severe side-effects. These data can potentially offer patients an improved quality of life during cancer therapy.

Takeda M, Kawahara H, Ogawa M, et al.
Reevaluation of Preoperative Chemoradiotherapy for Clinical T3 Lower Rectal Cancer: A Multicenter Collaborative Retrospective Clinical Study.
Anticancer Res. 2019; 39(6):3047-3052 [PubMed] Related Publications
AIM: This study aimed to re-evaluate the usefulness of preoperative chemoradiotherapy for clinical T3 lower rectal cancers without lateral lymph node metastasis.
PATIENTS AND METHODS: Between 2010 and 2014, 132 patients with clinical T3 lower rectal cancer without lateral lymph node metastasis, 80 years of age or younger, who underwent curative resection at four Jikei University Hospitals were enrolled into this retrospective study. Of these, 22 patients received chemoradiotherapy (CRT) before surgery, 16 patients received intensive chemotherapy after surgery without preoperative CRT, and 94 patients underwent neither preoperative CRT nor intensive chemotherapy after surgery including 47 patients with postoperative oral chemotherapy for pathological diagnosis of stage III.
RESULTS: The 3-year disease-free survival (DFS) of the 22 patients who received preoperative CRT was 95.5%, whereas that of the 94 patients who received neither preoperative CRT nor intensive chemotherapy was 72.0% (p=0.024). However, there was no significant difference in 5-year DFS between the two groups. No significant difference was identified in DFS between the 22 patients who received preoperative CRT and the 16 patients who received intensive chemotherapy after surgery without preoperative CRT.
CONCLUSION: Intensive chemotherapy after surgery seems to yield a similar prognosis to preoperative CRT in patients with clinical T3 lower rectal cancer without lateral lymph node metastasis.

Hatakeyama K, Nagashima T, Ohshima K, et al.
Mutational burden and signatures in 4000 Japanese cancers provide insights into tumorigenesis and response to therapy.
Cancer Sci. 2019; 110(8):2620-2628 [PubMed] Free Access to Full Article Related Publications
Tumor mutational burden (TMB) and mutational signatures reflect the process of mutation accumulation in cancer. However, the significance of these emerging characteristics remains unclear. In the present study, we used whole-exome sequencing to analyze the TMB and mutational signature in solid tumors of 4046 Japanese patients. Eight predominant signatures-microsatellite instability, smoking, POLE, APOBEC, UV, mismatch repair, double-strand break repair, and Signature 16-were observed in tumors with TMB higher than 1.0 mutation/Mb, whereas POLE and UV signatures only showed moderate correlation with TMB, suggesting the extensive accumulation of mutations due to defective POLE and UV exposure. The contribution ratio of Signature 16, which is associated with hepatocellular carcinoma in drinkers, was increased in hypopharynx cancer. Tumors with predominant microsatellite instability signature were potential candidates for treatment with immune checkpoint inhibitors such as pembrolizumab and were found in 2.8% of cases. Furthermore, based on microarray analysis, tumors with predominant signatures were classified into 2 subgroups depending on the expression of immune-related genes reflecting differences in the immune context of the tumor microenvironment. Tumor subpopulations differing in the content of infiltrating immune cells might respond differently to immunotherapeutics. An understanding of cancer characteristics based on TMB and mutational signatures could provide new insights into mutation-driven tumorigenesis.

Yumimoto K, Sugiyama S, Mimori K, Nakayama KI
Potentials of C-C motif chemokine 2-C-C chemokine receptor type 2 blockers including propagermanium as anticancer agents.
Cancer Sci. 2019; 110(7):2090-2099 [PubMed] Free Access to Full Article Related Publications
Inflammation plays an essential role in the development and progression of most cancers. Chemokine C-C motif chemokine 2 (CCL2) and its receptor C-C chemokine receptor type 2 (CCR2) constitute a key signaling axis in inflammation that has recently attracted much interest on the basis of evidence showing its association with cancer progression. Propagermanium (3-oxygermylpropionic acid polymer) is an organogermanium compound that is given for the treatment of hepatitis B in Japan and which inhibits the CCL2-CCR2 signaling pathway. Herein, we review the importance of the CCL2-CCR2 axis as a target in cancer treatment as shown by studies in mice and humans with pharmacological agents including propagermanium.

Akamatsu H, Ninomiya K, Kenmotsu H, et al.
The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV.
Int J Clin Oncol. 2019; 24(7):731-770 [PubMed] Free Access to Full Article Related Publications
According to rapid development of chemotherapy in advanced non-small cell lung cancer (NSCLC), the Japan Lung Cancer Society has been updated its own guideline annually since 2010. In this latest version, all of the procedure was carried out in accordance with grading of recommendations assessment, development and evaluation (GRADE) system. It includes comprehensive literature search, systematic review, and determination of the recommendation by multidisciplinary expert panel which consisted of medical doctors, pharmacists, nurses, statisticians, and patients from patient advocacy group. Recently, we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors. Thus, the guideline proposes to categorize patients into three entities: (1) driver oncogene-positive, (2) PD-L1 ≥ 50%, and (3) others. Based on this subgroup, 31 clinical questions were described. We believe that this attempt enables clinicians to choose appropriate treatment easier. Here, we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC, stages IV.

Ozaki S, Handa H, Saitoh T, et al.
Evaluation of the Revised International Staging System (R-ISS) in Japanese patients with multiple myeloma.
Ann Hematol. 2019; 98(7):1703-1711 [PubMed] Related Publications
In spite of recent development in the treatment armamentarium for multiple myeloma, overall survival (OS) still depends on risk status and sensitivity to treatment of each patient. We have evaluated the clinical relevance of the Revised International Staging System (R-ISS) by comparing it with the original ISS in 718 Japanese patients. The distribution of patients according to response was similar between the ISS and R-ISS stages. Treatment response was greatly influenced by initial treatment modalities and deeper response was observed more frequently in transplanted patients. The R-ISS discriminated the difference in OS between the stages more distinctly than the ISS (p = 9.0 × 10

Shitara K, Yodo Y, Iino S
A Phase I Study of Napabucasin Plus Paclitaxel for Japanese Patients With Advanced/Recurrent Gastric Cancer.
In Vivo. 2019 May-Jun; 33(3):933-937 [PubMed] Free Access to Full Article Related Publications
AIM: To report results from the first phase I study of napabucasin plus paclitaxel in Japanese patients with pre-treated unresectable/recurrent gastric cancer.
PATIENTS AND METHODS: Patients received napabucasin (480 mg bid) plus paclitaxel [80 mg/m
RESULTS: Six patients were enrolled. Paclitaxel had a minimal effect on napabucasin pharmacokinetics and median plasma paclitaxel concentrations were similar in combination and monotherapy. No dose-limiting toxicities were observed. There were no grade 4/5 adverse events. Partial response, stable disease and progressive disease were reported in two patients each.
CONCLUSION: Napabucasin plus paclitaxel was well-tolerated in Japanese patients with gastric cancer.

Shin J, Kunisawa S, Fushimi K, Imanaka Y
Effects of preoperative oral management by dentists on postoperative outcomes following esophagectomy: Multilevel propensity score matching and weighting analyses using the Japanese inpatient database.
Medicine (Baltimore). 2019; 98(17):e15376 [PubMed] Related Publications
The purpose of this study was to investigate the effects of preoperative oral management (POM) by dentists on the incidence of postoperative pulmonary complications (PPCs), length of hospital stay, medical costs, and days of antibiotics administration following both open and thoracoscopic esophagectomy.Dental plaque is an established risk factor for postoperative pneumonia, which could be reduced by POM. However, few clinical guidelines for cancer treatment, including those for esophageal cancer, recommend POM as routine perioperative care.We extracted data of esophagectomy cases from the Japanese Diagnosis Procedure Combination database. We subsequently conducted propensity score (PS) analyses for multilevel data, including matching, inverse probability of treatment weighting (IPTW), and standardized mortality ratio weighting (SMRW), to estimate the effect of POM by dentists on the outcomes of esophagectomy.We analyzed 3412 esophagectomy cases of which 812 were open, and 2600 were thoracoscopic surgery. In IPTW analysis to estimate the average treatment effect, the risk difference of postoperative aspiration pneumonia ranged from -2.49% to -2.02% between the POM and control groups of both open and thoracoscopic esophagectomy cases. IPTW analyses indicated that the total medical costs of thoracoscopic esophagectomy were reduced by 221,200 to 253,100 Japanese Yen (equivalent to about $2000-$2200). In PS matching and SMRW analyses to estimate average treatment effect on treated, there was no difference in outcomes between the POM and control groups.Our results suggested that in patients undergoing open or thoracoscopic esophagectomy, POM by dentists prevented the occurrence of postoperative aspiration pneumonia. It could also reduce the total medical costs of thoracoscopic esophagectomy. Thus, POM by dentists can be considered as a routine perioperative care for all patients undergoing esophagectomy, regardless of the expected risk for PPC.

Nagamatsu Y, Oze I, Aoe K, et al.
Physician requests by patients with malignant pleural mesothelioma in Japan.
BMC Cancer. 2019; 19(1):383 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed.
METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content.
RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients.
CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.

Ota A, Fujisawa A, Kawada K, Yatsuya H
Recent Status and Methodological Quality of Return-to-Work Rates of Cancer Patients Reported in Japan: A Systematic Review.
Int J Environ Res Public Health. 2019; 16(8) [PubMed] Free Access to Full Article Related Publications
Cancer patients' return-to-work rates in Japan and their methodological quality have been little reported. We conducted a systematic review to explore the recent return-to-work rates and to assess the methodological quality of the existing literature. We selected 13 papers (2 in English and 11 in Japanese) published between 2005 and 2017. The return-to-work rates ranged from 53.8% to 95.2%. Of the selected papers, 12 papers employed a cross-sectional design, possessing high risk of selection bias due to participant selection. A total of 8 papers did not fully report the subjects' sex, age, employment status at cancer diagnosis, cancer site, stage, and treatment, suggesting high risk of selection bias due to confounding variables. High or unclear risk of attrition bias due to incomplete outcome data was detected in 12 papers in which data on return to work were not collected from all participants. High risk of reporting bias due to selective outcome reporting was pointed out in 6 studies in which the subjects' employment status at return to work or the duration between cancer diagnosis and assessment of return to work was unclear. Future studies must reduce the risk of selection, attrition, and reporting biases for specifying accurate return-to-work rates.

Yamaguchi M, Suzuki R, Miyazaki K, et al.
Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin.
Ann Hematol. 2019; 98(7):1647-1655 [PubMed] Related Publications
Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients' fitness for steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65-75%) and 34% (95% CI, 21-47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P < 0.001). Despite the advent of new treatments for ENKL, OS remains unfavorable in extranasal NKTCL. A more effective therapy is needed for extranasal NKTCL.

Tamura T, Hishida A, Wakai K
Coffee consumption and liver cancer risk in Japan: a meta-analysis of six prospective cohort studies.
Nagoya J Med Sci. 2019; 81(1):143-150 [PubMed] Free Access to Full Article Related Publications
Previous epidemiological studies have shown that coffee consumption may reduce liver cancer risk. The present study aimed to summarize the evidence for this association in the Japanese population by performing a meta-analysis of the results of relevant cohort studies conducted in Japan. We searched studies published prior to September 1, 2018 in PubMed. Extracted data were analyzed using a random effects model. A total of six cohort studies from five publications were included in the final analysis. The pooled estimate of relative risk with 95% confidence interval (CI) for the group with highest coffee consumption was 0.50 (95% CI: 0.38-0.66,

Yasui M, Kawahara T, Izumi K, et al.
Androgen receptor mRNA expression is a predictor for recurrence-free survival in non-muscle invasive bladder cancer.
BMC Cancer. 2019; 19(1):331 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Non-muscular invasive bladder cancer (NMIBC) has a high risk of recurrence. As androgen receptor (AR) reportedly affects bladder cancer, we assessed the correlation between NMIBC recurrence and tumor AR expression in Japanese patients.
METHODS: We retrospectively reviewed 53 specimens of non-metastatic NMIBC, with recurrence-free survival (RFS) as the primary endpoint. We used real-time quantitative polymerase chain reaction to quantify AR mRNA expression. Kaplan-Meier product-limit estimators were used to assess RFS distribution, log-rank tests to analyze differences in RFS between high- and low-risk groups; and multivariate analyses of AR mRNA expression and other clinicopathological factors to predict independent factors for RFS.
RESULTS: The high AR mRNA-expressing group (n = 43) tended to have a longer median RFS (not reached) than did the low-AR group (n = 10; 9.04 months; P = 0.112). Multivariate analysis showed female sex (hazard ratio [HR]: 7.360, 95% CI: 1.649-32.856, P = 0.009), tumor size ≥3 cm (HR: 23.697, 95% CI: 4.383-128.117, P < 0.001) and low AR mRNA expression (HR: 0.202, 95% CI: 0.048-0.841, P = 0.028) to be independent predictors of shorter RFS.
CONCLUSION: Our study showed that low AR mRNA expression level is an independent risk factor for RFS in Japanese patients with NMIBC. Further studies are necessary but AR expression might be a new indicator of recurrence of NMIBC.

Yamazaki N, Kiyohara Y, Uhara H, et al.
Long-term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma.
Cancer Sci. 2019; 110(6):1995-2003 [PubMed] Free Access to Full Article Related Publications
The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long-term follow up of a single-arm, open-label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post-hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment-related adverse events (TRAE), including select immune-related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3-year OS rate was 43.5%, and the 3-year PFS rate was 17.2%. A long-term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long-term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.

Yoshimatsu K, Ishibashi K, Koda K, et al.
A Japanese multicenter phase II study of adjuvant chemotherapy with mFOLFOX6/CAPOX for stage III colon cancer treatment after D2/D3 lymphadenectomy.
Surg Today. 2019; 49(6):498-506 [PubMed] Related Publications
PURPOSE: A phase II trial was conducted to investigate the benefit of oxaliplatin-based adjuvant chemotherapy in Japanese stage III colon cancer patients.
METHODS: Eligible patients were scheduled to receive 12 cycles of mFOLFOX6 or 8 cycles of CAPOX in adjuvant settings. The primary endpoint was the 3-year disease-free survival (DFS). Cox proportional hazards regression was performed to identify risk factors for a worse DFS.
RESULTS: A total of 130 patients, including 73 patients receiving mFOLFOX6 and 57 patients receiving CAPOX, were enrolled from 16 institutions between April 2010 and April 2014. The 3-year DFS was 82.2%, exceeding the expected primary endpoint of 81.7%. The 3-year DFS tended to be higher in patients receiving mFOLOFOX6 than in those receiving CAPOX (mFOLFOX6, 86.3%; CAPOX, 76.9%; P = 0.06). The 3-year DFS rates did not differ markedly based on the risk stratification (T1/T2/T3 N1 vs. T4 or N2) indicated by the IDEA COLLABORATION study (P = 0.22). In the multivariate analysis, stage IIIC (P = 0.046) and early discontinuation (P < 0.01) were identified as independent significant risk factors for a worse DFS.
CONCLUSION: Our findings represent the first positive results in a Japanese phase II trial of adjuvant chemotherapy with mFOLFOX6/CAPOX. Early discontinuation within 2 months was an independent risk factor for a shorter DFS.

Sato S, Nakamura M, Shimizu Y, et al.
The impact of emphysema on surgical outcomes of early-stage lung cancer: a retrospective study.
BMC Pulm Med. 2019; 19(1):73 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The presence of emphysema on computed tomography (CT) is associated with an increased frequency of lung cancer, but the postoperative outcomes of patients with pulmonary emphysema are not well known. The objective of this study was to investigate the association between the extent of emphysema and long-term outcomes, as well as mortality and postoperative complications, in early-stage lung cancer patients after pulmonary resection.
METHODS: The clinical records of 566 consecutive lung cancer patients who underwent pulmonary resection in our department were retrospectively reviewed. Among these, the data sets of 364 pathological stage I patients were available. The associations between the extent of lung emphysema and long-term outcomes and postoperative complications were investigated. Emphysema was assessed on the basis of semiquantitative CT. Surgery-related complications of Grade ≥ II according to the Clavien-Dindo classification were included in this study.
RESULTS: Emphysema was present in 63 patients. The overall survival and relapse-free survival of the non-emphysema and emphysema groups at 5 years were 89.0 and 61.3% (P < 0.001), respectively, and 81.0 and 51.7%, respectively (P < 0.001). On multivariate analysis, significant prognostic factors were emphysema, higher smoking index, and higher histologic grade (p < 0.05). Significant risk factors for poor recurrence-free survival were emphysema, higher smoking index, higher histologic grade, and presence of pleural invasion (P < 0.05). Regarding Grade ≥ II postoperative complications, pneumonia and supraventricular tachycardia were more frequent in the emphysema group than in the non-emphysema group (P = 0.003 and P = 0.021, respectively).
CONCLUSION: The presence of emphysema affects the long-term outcomes and the development of postoperative complications in early-stage lung cancer patients.

Tomita Y, Fukasawa S, Shinohara N, et al.
Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup 3-year follow-up analysis from the Phase III CheckMate 025 study.
Jpn J Clin Oncol. 2019; 49(6):506-514 [PubMed] Related Publications
BACKGROUND: Nivolumab treatment resulted in superior efficacy and safety versus everolimus treatment in the 2-year follow-up of the CheckMate 025 Phase III study, with consistent results in the global population and the Japanese population. Here, we report the 3-year follow-up in both groups.
METHODS: Patients were randomized 1:1 to nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10 mg orally once daily until progression/intolerable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included objective response rate, progression-free survival, safety and patient-reported quality of life.
RESULTS: Of 410 and 411 patients randomized to nivolumab and everolimus, 37 and 26 were Japanese, respectively. The median OS for the global population was 25.8 months with nivolumab and 19.7 months with everolimus (hazard ratio 0.74; 95.5% confidence interval [CI]: 0.63-0.88; P = 0.0005); in the Japanese population, median OS was 45.9 months and not reached (hazard ratio 1.08; 95% CI: 0.50-2.34; P = 0.85), respectively. The investigator-assessed objective response rate was 26% versus 5% with nivolumab versus everolimus (odds ratio [OR] 6.19; 95% CI: 3.82-10.06) in the global population and 43% versus 8% in the Japanese population (OR 6.80; 95% CI: 1.60-28.91; P = 0.0035), respectively. The incidence of any-grade treatment-related adverse events was lower with nivolumab versus everolimus in both the global patient population (80% versus 89%) and the Japanese population (81% versus 100%).
CONCLUSIONS: At the 3-year follow-up, the efficacy and safety results of CheckMate 025 are generally consistent in the global and the Japanese populations.

Hamada S, Ichiyasu H, Ikeda T, et al.
Protective effect of bevacizumab on chemotherapy-related acute exacerbation of interstitial lung disease in patients with advanced non-squamous non-small cell lung cancer.
BMC Pulm Med. 2019; 19(1):72 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) is the most serious complication in lung cancer patients with pre-existing ILD receiving chemotherapy. The role of vascular endothelial growth factor (VEGF) in pathogenesis of AE-ILD is conflicting. The influence of bevacizumab (Bev), a monoclonal antibody against VEGF, on lung cancer patients with pre-existing ILD remains unclear. We examined the effect of Bev on reducing AE-ILD risk in non-squamous non-small cell lung cancer (NSCLC) patients receiving chemotherapy.
METHODS: We analysed incidence of AE-ILD and outcomes of 48 patients with advanced non-squamous NSCLC with ILD who received first-line chemotherapy with (Bev group, n = 17) and without (non-Bev group, n = 31) Bev between July 2011 and July 2016. Gray's test, which was competing risk analysis during the study period, was performed for both groups.
RESULTS: The most common regimen used for first-line chemotherapy was the combination of carboplatin plus pemetrexed (PEM) in both groups. The incidences of chemotherapy-related AE-ILD 120 days after first-line chemotherapy initiation were significantly lower in the Bev than in the non-Bev groups (0% vs. 22.6%, p = 0.037, Gray's test). However, there were no differences in development of progressive disease of lung cancer and other events as the competing risk factors of AE-ILD between the two groups. Only patients receiving PEM-containing regimens also showed a significant difference in the incidence of AE-ILD between the two groups (p = 0.044). The overall-cumulative incidence of AE-ILD during the first-line and subsequent chemotherapy was 29.2% (14 of the 48). The median progression-free survival was significantly longer in the Bev than in the non-Bev groups (8.0 vs. 4.3 months, p = 0.026).
CONCLUSIONS: The addition of Bev to chemotherapy regimens may reduce the risk of chemotherapy-related AE-ILD in patients with lung cancer.

Sasaki A, Hirato J, Hirose T, et al.
Review of ependymomas: assessment of consensus in pathological diagnosis and correlations with genetic profiles and outcome.
Brain Tumor Pathol. 2019; 36(2):92-101 [PubMed] Related Publications
We focused on histological and immunohistochemical characteristics of ependymoma (EPN) with molecular profiles to develop more reproducible criteria of the diagnosis. Three expert neuropathologists reviewed the pathology of 130 samples from the Japan Pediatric Molecular Neuro-Oncology Group study. Confirmed cases were assessed for histology, surrogate markers, molecular subgrouping, and survival data. We reached a consensus regarding the diagnosis of EPNs in 100% of spinal cord tumors and 93% of posterior fossa (PF) tumors that had been diagnosed as EPNs by local pathologists, whereas we reached a consensus regarding only 77% of the local diagnosis of supratentorial (ST) EPNs. Among the PF-EPNs, most of anaplastic ependymomas (AEPNs) were defined as EPN-A by methylation profiling, which was significantly correlated with the subgroup assignment. Regarding prognosis, the overall survival of patients with PF-EPN was significantly better than that of patients with PF AEPN (p = 0.01). Histologically, all ependymoma, RELA fusion-positive (EPN-RELA) qualified as Grade III. Both L1 cell adhesion molecule and nuclear factor kappaB p65 antibodies showed good sensitivity for detecting EPN-RELA. This study indicated that the expert consensus pathological diagnosis could correlate well with the molecular classifications in EPNs. ST EPNs should be diagnosed more carefully by histological and molecular analyses.

Sakai H, Yamada SI, Gibo T, et al.
A retrospective analysis of the prevalence of dental diseases in patients with digestive system cancers.
Medicine (Baltimore). 2019; 98(13):e14771 [PubMed] Free Access to Full Article Related Publications
The relationship between dental diseases and the prevalence of digestive system cancers remains unclear. The aim of the present study was to examine the prevalence of dental diseases in patients treated for digestive system cancers.The medical and dental records of patients treated for digestive system cancers were retrospectively reviewed, and the results obtained (decayed/filled/missing teeth [DMFT] indices and community periodontal index [CPI] codes) were compared with data from the national survey of dental diseases in order to investigate the relationship between oral health and digestive system cancers.DMFT, D, and F indices were significantly lower, while the M index was slightly higher in digestive system cancer patients than in the national survey. The proportions of individuals with more than 20 residual teeth and denture wearers were significantly lower in cancer patients than in the national survey. The prevalence of periodontitis (CPI codes 3 and 4) and severe periodontitis (CPI code 4) were significantly higher in cancer patients than in the national survey.The present results showed that digestive system cancers were closely associated with multi-tooth loss and/or a low denture-wearing rate. The prevalence of severe periodontitis was also found to be higher in cancer patients. These results suggest that periodontitis and associated multi-tooth loss play a potential role in digestive system cancers.

Nagahama M, Ozeki T, Suzuki A, et al.
Association of lenvatinib trough plasma concentrations with lenvatinib-induced toxicities in Japanese patients with thyroid cancer.
Med Oncol. 2019; 36(5):39 [PubMed] Related Publications
The aim of this study was to examine the association of lenvatinib-induced adverse events with the trough plasma concentration (C

Yonemura Y, Canbay E, Wakama S, et al.
Prognostic Factors of Malignant Peritoneal Mesothelioma Experienced in Japanese Peritoneal Metastasis Center.
Gan To Kagaku Ryoho. 2019; 46(2):395-399 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment.
METHODS: Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively.
CONCLUSIONS: Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.

Yonemura Y, Canbay E, Wakama S, et al.
Analysis of Treatment Failure after Complete Cytoreductive Surgery for Peritoneal Metastasis from Appendiceal Mucinous Neoplasm at a Japanese High Volume Center for Peritoneal Surface Malignancy.
Gan To Kagaku Ryoho. 2019; 46(2):251-258 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Treatment failure after complete cytoreduction for appendiceal mucinous carcinoma peritonei (AMCP)has not been fully investigated. The present study was performed to clarify the risk factor for recurrence after complete cytoreduction for AMCP.
METHODS: A total of 400 patients with AMCP who underwent complete cytoreductive surgery combined with perioperative chemotherapy were investigated.
RESULTS: Documented recurrence was developed in 135 (33.8%)patients. The 5- and 10-year progression-free survival was 51% and 49%, respectively. By multivariate analysis, histological subtype of peritoneal disease(high-grade AMCP[AMCP-H]and AMCP-H with signet ring cells), serum CA19- 9 level, and PCIB20 were significantly associated with reduced progression-free survival. In contrast, histologic subtype of mucin without epithelial cells(MWEC)showed the lowest risk for recurrence. Eighty-six patients had localized intra-abdominal recurrence, and 42 patients had diffuse peritoneal recurrence. Recurrence was found in the various peritoneal sectors. Eighty-one patients underwent complete cytoreduction for the recurrence, and the overall survival 5-year survival rate after secondary cytoreduction was 49%.
CONCLUSIONS: Risk factors for recurrence were histologic subtype, PCI cutoff level, and serum CA19-9 levels. Aggressive second attempt of cytoreduction in patients with localized recurrence improved the survival.

Sagawa M, Machii R, Nakayama T, et al.
The Prefectural Participation Rates of Lung Cancer Screening Had a Negative Correlation with the Lung Cancer Mortality Rates
Asian Pac J Cancer Prev. 2019; 20(3):855-861 [PubMed] Related Publications
Background: The participation rate is one of the most important indexes in the cancer screening. Historically in Japan, each local government has developed their own equations to calculate the subjects for population-based screening, which were different from each other, and therefore the participation rates of screening were not comparable. Recently, local governments were ordered to use the standardized equation in reporting data, which made it possible to compare the participation rates of cancer screening nationwide for the first time. We therefore investigated the correlation between the prefectural lung cancer mortality and several indicators of lung cancer screening. Methods: The prefectural participation rates of lung, gastric and colonic cancer screening, test positive rates, attendance rates for further examination, lung cancer detection rates and positive predictive values of lung cancer screening were collected from “Cancer Registration and Statistics” of the National Cancer Research Center website. The age-adjusted lung, gastric and colonic cancer mortality rates, smoking rates were also collected. The EZR software program was used for statistical analyses. Results: The participation rates of lung cancer screening had a strong positive correlation with the participation rates of gastric/colonic cancer screening (P<0.001). The prefectural lung cancer mortality rates had a moderate to weak negative correlation with the participation rates of lung cancer screening (P=0.009). A little correlation was noted between other quality assurance indicators of lung cancer screening and lung cancer mortality rates. Conclusion: These results suggested that participating in lung cancer screening might help reduce lung cancer mortality rates in some extent.

Shiotani A, Ishikawa H, Mutoh M, et al.
Impact of Diarrhea after Drinking on Colorectal Tumor Risk: A Case Control Study
Asian Pac J Cancer Prev. 2019; 20(3):795-799 [PubMed] Related Publications
Background: Recently, the number of colorectal cancer (CRC) cases in Japan has been increasing, and is strongly influenced by alcohol consumption. On the other hand, there are several reports suggesting a relationship between bowel movement (constipation and diarrhea) and CRC development. Moreover, it is generally known that diarrhea may occur after drinking. However, the mechanism by which drinking alcohol increases CRC is not fully clarified yet. We hypothesized that diarrhea after drinking may play an important role in colorectal carcinogenesis. Methods: We examined the presence of diarrhea after drinking and further evaluated the correlation of diarrhea after drinking with the incidence of colorectal tumors. To obtain the status of the feces, a self-recorded questionnaire survey was administered using the dietary-recording method. Blood samples were obtained to analyze the ALDH2 Glu504Lys and ADH1B His48Arg polymorphisms. Results: The participants were 417 patients who had undergone a total colonoscopy. The control was selected from 186 patients who underwent a medical checkup at the same hospital during the same time period. The odds ratio for all subjects was 2.1 (95% CI: 1.18 - 3.80), and that for heavy drinkers was 4.2 (1.48 - 11. 90). Conclusions: The results demonstrated that those who have diarrhea after drinking possess a high risk of developing colon tumors.

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