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Japanese Journal of Clinical Oncology

Japanese Journal of Clinical Oncology - RSS feed of current issue

Mammography is the only method of breast cancer screening that has established evidence of a mortality reduction. However, mammography does not achieve sufficient accuracy in the high-density breasts of patients <50 years of age. In 2009, the US Preventive Services Task Force revised its recommendation for breast cancer screening in women aged 40–49 years from Grade B to C because the net benefit was relatively small for this age bracket. The net benefit of screening is the sum of benefits and harm and should always be monitored especially in population screening. A high recall rate, an inefficient number needed to invite for screening to prevent one breast cancer death, a high false-positive rate and unnecessary additional imaging for women aged 40–49 years are great concerns of mammography screening. Overdiagnosis is also a detriment of mammography screening; however, it may have a limited effect on women aged 40–49 years. Establishment of new evidence for breast cancer screening, such as ultrasonography screening, is needed in order to create a more effective screening system.


Objective

Human epidermal growth factor receptor 2 (HER2) gene amplification is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-human epidermal growth factor receptor 2 agents. Human epidermal growth factor receptor 2 somatic mutations have been reported in patients without human epidermal growth factor receptor 2 gene amplification. Since these are activating mutations, these patients may also benefit from human epidermal growth factor receptor 2-targeted drugs.

Methods

In this study, we searched for human epidermal growth factor receptor 2 mutations in a group of 286 Japanese breast cancer patients with human epidermal growth factor receptor 2-negative tumors. The activating mutations of human epidermal growth factor receptor 2 identified were analyzed by direct Sanger sequencing of two major areas: the extracellular domain at 309–310 and the kinase domain between 755 and 781.

Results

Two tumors were found to have a human epidermal growth factor receptor 2 somatic mutation; one with I767M mutation and another with D769Y. No mutation was observed in the extracellular domain. One of these patients with human epidermal growth factor receptor 2 mutation recurred early with liver metastasis.

Conclusions

Better knowledge of human epidermal growth factor receptor 2 mutation status will help us to choose personalized molecular targeted therapy for use in human epidermal growth factor receptor 2-negative Japanese breast cancer patients.


Objective

In vitro chemotherapy response assays are not widely accepted in making decisions regarding cytotoxic drugs. To evaluate the usefulness of chemotherapy response assays in breast cancer, we compared the chemotherapy response assay results according to subtypes. Human epidermal growth factor receptor-2 and Ki67 associated with chemosensitivity were also analyzed.

Methods

Four hundred and ninety-six patients were enrolled, and chemotherapy response assays based on adenosine triphosphate were performed in 500 tumors. Patients were classified as five subtypes: luminal A, luminal B/human epidermal growth factor receptor-2 negative, luminal B/human epidermal growth factor receptor-2 positive, human epidermal growth factor receptor-2 and triple negative. The cell death rate for various drugs was calculated.

Results

The mean cell death rate of the luminal A subtype was the lowest, and the mean cell death rates of the human epidermal growth factor receptor-2 and triple-negative subtypes were the highest for all tested drugs, except 5-fluorouracil and methotrexate. The cell death rate differed significantly among the subtypes in the types of drugs (doxorubicin, epirubicin, paclitaxel, docetaxel, gemcitabine, vinorelbine and cisplatin). In triple-negative tumors, the mean cell death rate of cisplatin was the highest among the tested drugs, and which was not observed in the other subtypes. Human epidermal growth factor receptor-2 positive tumors are associated with higher cell death rates for anthracyclines. High Ki67 expression (a cutoff of 14%) was associated with a high response in several tested drugs including epirubicin, paclitaxel, docetaxel, gemcitabine, vinorelbine and cisplatin.

Conclusions

Our findings suggest that in vitro chemoresponse assays for breast tumors could effectively reflect the tumor response to chemotherapies observed in neoadjuvant settings.


Objective

Medical oncology in Japan has a relatively short history, with specialist certification starting in 2006, resulting in 867 certified medical oncologists as of 2014. Although the national government has appointed 397 Designated Cancer Care Hospitals, little is known about the actual situations of medical oncology services at these institutions.

Methods

Questionnaires regarding the presence of a medical oncology department, the number of physicians in the department, the presence of certified medical oncologists and the degree of the medical oncologists' responsibilities for drug therapies in adults with solid cancers were sent to all 397 institutions between 21 January and 1 May 2013.

Results

The response rate was 68.0%. Among the responses, 39.4% of the institutions had medical oncology departments with a median of three physicians. Most of the medical oncology departments were primarily responsible, as evaluated according to patient number, for the treatment of limited disease categories. The medical oncologists were significantly more responsible for molecular-targeted therapy than for chemotherapy in head and neck cancer or for cytokine therapy in renal cell carcinoma. The wide variety of adverse events associated with molecular-targeted therapy might have enhanced the roles of medical oncologists. As the proportion of hospitals with a medical oncology department increased according to the number of certified medical oncologists working at the institution, cultivating medical oncologists seems to be an urgent task for advancing medical oncology in Japan.

Conclusions

The present study provides fundamental data for the future development of medical oncology in Japan. The present study is to uncover the current situation of medical oncology in Japan.


Objective

The association between meat consumption and colorectal cancer remains inconsistent among Asians. The present study systematically evaluated and meta-analyzed epidemiologic studies on the association between consumption of total and specific meats and colorectal cancer risk among Japanese.

Methods

Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented with manual searches. The associations were evaluated based on the strength of evidence, the magnitude of association and biologic plausibility. A meta-analysis was performed according to total meat, red and processed meat as well as poultry and site-specific cancers.

Results

Six cohort studies and 13 case–control studies were identified. In cohort studies, most investigations found no association between total meat consumption and colon/rectal cancer, and several studies showed a weak-to-moderate positive association of red meat and processed meat consumption with colon/rectal cancer. The majority of case–control studies showed no association between total meat consumption and colon and rectal cancer; however, several ones reported a weak-to-strong positive association of red and processed consumption with colon and rectal cancer. In meta-analysis, the summary relative risks (95% confidence interval) for the highest versus lowest categories of red meat consumption were 1.16 (1.001–1.34) and 1.21 (1.03–1.43) for colorectal and colon cancer, respectively, and those for processed meat consumption were 1.17 (1.02–1.35) and 1.23 (1.03–1.47) for colorectal and colon cancer, respectively. Poultry consumption was associated with lower risk of rectal cancer; summary relative risk (95% confidence interval) was 0.80 (0.67–0.96).

Conclusions

High consumption of red meat and processed meat possibly increases risk of colorectal cancer or colon cancer among the Japanese population.


Objective

This study was aimed to examine how well readers of newspapers understand cancer survival rate data, and the effect of this understanding on their behavioral intent.

Methods

We recruited 1950 persons who were 20 years old or older registered with a market research company. Participants were randomly divided into 10 groups; 9 were assigned one of nine newspaper articles, and the remaining group was assigned the excerpt of the official Association of Clinical Cancer Centers web pages. The primary outcome was the proportion of respondents with ‘sufficient understanding’, who gave 70% or more correct answers on a 10-item knowledge question.

Results

The proportion of participants with sufficient understanding varied across the groups (range: 0.8–22.1%, overall, P < 0.001). Only around 15% of participants answered that they would consider other hospitals in a scenario where the only hospital in the participants' area had a 5-year survival of 5% or less, and answers did not significantly vary between groups (range: 11.1–21.0%, overall P = 0.77).

Conclusions

The level of understanding of cancer survival rate varied by variation in media reporting. However, the effect of behavioral intent on hospital choice did not differ between articles.

Trial registration

UMIN CTR UMIN000004885.


Objective

In Japan, cisplatin/5-fluorouracil 80/800 (cisplatin 80 mg/m2, 5-fluorouracil 800 mg/m2) is widely used to treat recurrent/metastatic squamous cell carcinoma of the head and neck, whereas cisplatin/5-fluorouracil 100/1000 (1000 mg/m2/24 h by continuous intravenous infusion on Days 1–4 plus cisplatin 100 mg/m2 on Day 1 in 3-week cycles) is the standard treatment in Europe and North America.

Methods

We prospectively evaluated the feasibility of cisplatin/5-fluorouracil 100/1000 in Japanese patients enrolled in the global Phase 3 study of panitumumab 9 mg/kg combined with cisplatin/5-fluorouracil 100/1000 (Arm 1) versus cisplatin/5-fluorouracil 100/1000 alone (Arm 2).

Results

Twenty Japanese patients were enrolled and received treatment (Arm 1, n = 13; Arm 2, n = 7). Grade 3/4 adverse events included neutropenia, hypomagnesemia, stomatitis, hyponatremia, paronychia, febrile neutropenia, decreased appetite and hypokalemia. There were no fatal adverse events. Median overall survival was not estimable in Arm 1 and 15.4 months in Arm 2. Median progression-free survival was 6.9 months in Arm 1 and 5.7 months in Arm 2. The median number of infusions (cycles) of cisplatin was 5 in Arm 1 and 4 in Arm 2; the median number of infusions (cycles) of 5-fluorouracil was 6 in both arms. The mean administered dose for cisplatin was 93.6 mg/m2 in Arm 1 and 97.2 mg/m2 in Arm 2, and 3732.6 and 3880 mg/m2 in Arm 1 and Arm 2, respectively, for 5-fluorouracil.

Conclusions

These results suggested that cisplatin/5-fluorouracil 100/1000 was feasible for recurrent/metastatic squamous cell carcinoma of the head and neck in Japanese patients.


Objective

Comprehensive assessment of perceived concerns can be used to guide supportive care appropriate to individual cancer patients. This study sought to determine the prevalence of cancer patients' concerns and the degree to which these concerns contribute to patients' quality of life.

Methods

Participants were patients with all types of cancer, who completed an Internet survey questionnaire regarding comprehensive concerns about physical, psychological, psychosocial and economic aspects of having cancer. The questionnaire was based on the newly developed Comprehensive Concerns Assessment Tool and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.

Results

We obtained complete data from 807 patients. Factors related to ‘self-management’ concerns were the most common (61.2%), followed by concerns about ‘psychological symptoms’ (48.5%), ‘medical information’ (46.2%), ‘daily living’ (29.9%), ‘pain’ (17.6%), ‘constipation’ (15.6%) and other ‘physical symptoms’ (15.2%). Multiple regression analysis revealed that all concerns except those about ‘medical information’ significantly contributed to quality of life.

Conclusions

Cancer patients' concerns were shown to be multidimensional and significantly associated with quality of life. Thus, assessment of patients' concerns should be multidimensional in nature, and a multidisciplinary care team should help patients improve their quality of life.


Objective

We report on the short and late morbidity and mortality of ileal conduit and neobladder after radical cystectomy with their associated risk factors.

Methods

We retrospectively collected data on 308 non-metastatic bladder cancer patients who underwent radical cystectomy with either ileal conduit or neobladder for a curative intent from January 1999 to December 2011. Post-operative morbidity and mortality of 30-day (early) and 90-day (late) complication with their risk factors were examined in association with different types of urinary diversion. A comparative analysis using propensity-score matching was performed with matching variables of age, sex, number of underlying diseases and pathologic T and N stages, lymph node dissection, operative time and time of surgical year for comparison of the early and late morbidities between ileal conduit and neobladder.

Results

During the median follow-up of 46.6 months, early and late morbidities were 29.5% (n = 91) and 19.8% (n = 61), and complication-related mortalities were 2.2 and 6.6%, respectively. The type of urinary diversion significantly affected only the late complications (early: neobladder 57 vs. ileal conduit 47, P = 0.096; late: neobladder 67 vs. ileal conduit 37, P < 0.001). However, after propensity-score matching, no significant differences in early and late morbidities were observed between neobladder and ileal conduit. For risk factors of morbidity, number of removed lymph node states and hypertension were independently significant for both early and late complications (P < 0.05).

Conclusions

The type of urinary diversion affected only late complication, however, results of the matching analysis showed no significant differences in early and late morbidities between neobladder and ileal conduit .


Objective

To assess health-related quality of life in the first year after laparoscopic radical prostatectomy compared with that after open radical prostatectomy.

Methods

The subjects were 105 consecutive patients with localized prostate cancer treated with laparoscopic radical prostatectomy between January 2011 and June 2012. Health-related quality of life was evaluated using the International Prostate Symptom Score, Medical Outcome Study 8-Items Short Form Health Survey (SF-8) and Expanded Prostate Cancer Index Composite at baseline and 1, 3, 6 and 12 months after surgery. Comparisons were made with data for 107 consecutive patients treated with open radical prostatectomy between October 2005 and July 2007.

Results

The International Prostate Symptom Score change was similar in each group. The laparoscopic radical prostatectomy group had a better baseline Medical Outcome Study 8-Items Short Form Health Survey mental component summary score and a better Medical Outcome Study 8-Items Short Form Health Survey physical component summary score at 1 month after surgery. In Expanded Prostate Cancer Index Composite, obstructive/irritative symptoms did not differ between the groups, but urinary incontinence was worse until 12 months after surgery and particularly severe after 1 month in the laparoscopic radical prostatectomy group. The rate of severe urinary incontinence was much higher in the laparoscopic radical prostatectomy group in the early period. Urinary bother was worse in the laparoscopic radical prostatectomy group at 1 and 3 months, but did not differ between the groups thereafter. Urinary function and bother were good after nerve sparing procedures and did not differ between the groups. Bowel and sexual function and bother were similar in the two groups.

Conclusion

Urinary function in the first year after laparoscopic radical prostatectomy is worse than that after open radical prostatectomy.


Hemorrhagic radiation cystitis is an example of a typical radiotherapy-induced adverse event. However, the optimal treatment for hemorrhagic radiation cystitis is not known. There are limited data regarding the use of argon plasma coagulation for hemorrhagic radiation cystitis. Here, we present the use of argon plasma coagulation using a gastrointestinal endoscope to treat hemorrhagic radiation cystitis. The patient was a 75-year-old male patient with hemorrhagic radiation cystitis due to external beam irradiation for prostate adenocarcinoma. Six years after radiotherapy, the patient presented with macroscopic hematuria over the preceding 4 months, and laboratory investigations revealed a low hemoglobin level. The hematuria was not controlled with 2 days of bladder irrigation using normal saline. Thus, argon plasma coagulation using an upper gastrointestinal endoscope was considered for treatment of the hemorrhagic radiation cystitis. The cystoscopic examination revealed diffuse radiation cystitis with oozing telangiectasia and coagula. All of the bleeding sites and telangiectasia were coagulated using argon plasma coagulation. Following treatment, the patient's clinical symptoms improved and did not recur. The hemoglobin level also recovered. No complications associated with the treatment were observed during the 6-month follow-up period. Thus, argon plasma coagulation using a gastrointestinal endoscope is a safe and effective treatment for hemorrhagic radiation cystitis.


To accelerate the completion of clinical trials, it is critical to obtain, at high rates, informed consent to participate from patients who are eligible. It is therefore important to know what factors affect the participation rates of eligible patients. Selection of effective chemotherapy for breast cancer and its successor selection of effective chemotherapy for breast cancer-CONFIRM are randomized controlled trials conducted for Japanese patients with chemotherapy-naïve metastatic breast cancer. These trials are intended to compare the current standard chemotherapeutic regimens in the first-line setting, which are taxanes for selection of effective chemotherapy for breast cancer and anthracyclines for selection of effective chemotherapy for breast cancer-CONFIRM, respectively, and an oral regimen of TS-1 in terms of overall survival. We are conducting prospective studies to identify the factors affecting the rates at which informed consent is obtained in selection of effective chemotherapy for breast cancer and breast cancer-CONFIRM. We are using a self-administered questionnaire that we have developed to collect information regarding patients' characteristics and attitude to clinical trials.