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Japanese Journal of Clinical Oncology Current Issue





Published: Thu, 13 Apr 2017 00:00:00 GMT

Last Build Date: Wed, 03 May 2017 05:45:08 GMT

 



IN THIS ISSUE

2017-04-13













Clinical outcome of definitive radiation therapy for superficial esophageal cancer

2017-02-23

Abstract
Objective
To analyze the clinical outcome of concurrent chemoradiotherapy in superficial esophageal cancer patients.
Methods
We retrospectively analyzed data for 123 patients with superficial esophageal cancer who received external beam radiotherapy without intracavitary brachytherapy plus systemic chemotherapy during 1998–2015. Elective nodal irradiation was not performed. The dosage to planning treatment volume was 60 Gy in 30 fractions. The main outcome measure was overall survival.
Results
Patient characteristics were as follows: median age, 66 (41–83) years; male/female ratio, 106/17; squamous cell carcinoma/other, 122/1; cT1a/cT1b, 27/96; cervical esophagus/upper thoracic esophagus/middle thoracic esophagus/lower thoracic esophagus, 7/9/66/41 and concurrent chemoradiotherapy/radiotherapy alone, 100/23. Cisplatin and 5-fluorouracil were the most commonly used agents (85%). At the last follow-up (median 60.5 months), 91 (74%) patients were alive. Complete response was achieved in 116 (94.4%) patients. The 5-year overall survival, progression-free survival and local control rates were 77.0, 46.9 and 62.7%, respectively, similar to that in the elderly patients (P = 0.878, 0.754 and 0.648, respectively). There were 55 failures: 42 local, 10 regional and 3 distant failures. Nine local and seven regional failures developed out-of-field. Thirty-eight local failures (90%) were successfully salvaged, of which 30 (71%) were salvaged via endoscopic removal; only 2 regional failures (20%) were salvaged. Fifteen G3 acute toxicities occurred. One pneumonitis (G3), one pneumothorax (G3) and two pericardial effusion (G2) were the late toxicities observed. There were no G4 toxicities or treatment-related deaths.
Conclusions
Concurrent chemoradiotherapy without intracavitary brachytherapy was effective and safe for superficial esophageal cancer, even in elderly patients.



Clinical utility of a self-administered questionnaire for assessment of hereditary gynecologic cancer

2017-02-23

Abstract
Background
A patient's medical history and familial cancer history are important information for assessing the risk of hereditary cancer. We have generated a self-administered questionnaire for patients with gynecologic cancer. This pilot study analyzed the usefulness of this questionnaire and the rates of patients that meet the Society of Gynecologic Oncology criteria in ovarian cancer and endometrial cancer patients.
Method
Ovarian or endometrial cancer patients were recruited for this study. After informed consent was obtained, participants completed the questionnaire. Genetic risks were assessed from the data of each patient's questionnaire by Society of Gynecologic Oncology guideline. Clinical and pathological findings were compared between the genetic risk groups.
Results
A total of 105 patients were identified with ovarian cancer and 56 patients with endometrial cancer eligible for this study. According to the Society of Gynecologic Oncology guideline, of the 105 ovarian cancer patients, 25 patients (23%) had a 20–25% risk and three patients (2.9%) had a 5–10% risk of hereditary breast and ovarian cancer syndrome. A further 22 patients (21%) had a 5–10% risk of Lynch syndrome. Two patients (1.9%) met the Amsterdam criteria II. Of 56 endometrial cancer patients, 24 patients (42.9%) had a 5–10% risk of Lynch syndrome. The endometrial cancer patients with genetic risk of Lynch syndrome were younger (mean age: 47.79) at diagnosis compared to patients without a genetic risk of Lynch syndrome (mean age: 57.91).
Conclusions
In this study, we were able to show that the newly designed questionnaire is a useful tool for evaluating cancer family history along with Society of Gynecologic Oncology criteria or Amsterdam criteria II. When considering the risk of Lynch syndrome for a patient with ovarian cancer, it is important to collect a second and third relative's family history.



Discomfort during bronchoscopy performed after endobronchial intubation with fentanyl and midazolam: a prospective study

2017-02-23

Abstract
Objective
Although endobronchial intubation during a bronchoscopic examination is useful for invasive procedures, it is not routine practice in Japan. The present study evaluated discomfort due to endobronchial intubation using fentanyl and midazolam sedation during bronchoscopy.
Methods
Thirty-nine patients were enrolled prospectively from November 2014 to September 2015 at Okayama University Hospital. Fentanyl (20 µg) was administered to the patients just before endobronchial intubation, and fentanyl (10 µg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire survey was administered 2 h after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: excellent (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question (‘Do you remember the bronchoscopic examination?’) was also asked. Predefined parameters (blood pressure, heart rate, oxygen saturation and complications) were recorded.
Results
The enrolled patients included 22 males and 17 females; their median age was 70 (range: 28–88) years. The patients received a mean dose of 47.9 µg of fentanyl (range: 30–90 µg) and 2.79 mg of midazolam (range: 1–7 mg). In total, 28 patients (71.7%) agreed to undergo a second bronchoscopic examination; the mean levels of discomfort and for the re-examination were 2.07 points each. About 41% of the patients remembered the bronchoscopic examination. No severe complications were reported.
Conclusion
Endobronchial intubation using fentanyl and midazolam sedation during an invasive bronchoscopic procedure might be recommended.
Clinical Trial Registration
UMIN000015578 in the UMIN Clinical Trials Registry



Significance of primary lesion resection in Stage IV breast cancer

2017-02-23

Abstract
Systemic treatment with drugs is administered to prolong survival and palliate symptoms in Stage IV breast cancer patients who have distant metastases at diagnosis. Surgical procedures for the primary tumor are not actively recommended in guidelines due to lack of evidence indicating prognostic benefit. Recently, several retrospective studies have shown primary tumor resection to prolong overall survival in patients with Stage IV breast cancer. Prospective randomized trials began enrolling patients to examine this possibility and two have already reported results. However, the results of these two trials were discordant. The first trial, conducted in India, reported negative effects of primary tumor resection after primary systemic therapy. A Turkish trial then obtained a positive effect of surgery as primary treatment. Several questions regarding the effects, timing, methods and eligibility for primary surgery have yet to be answered. Robust evidence, which is anticipated from other ongoing trials examining surgery for metastatic breast cancer, is eagerly awaited.



Isolated ACTH deficiency probably induced by autoimmune-related mechanism evoked with nivolumab

2017-02-18

Abstract
Nivolumab, an anti-programmed death-1 antibody, is a breakthrough treatment for several malignancies. Its specific adverse effects caused by autoimmunity are termed immune-related adverse events, which involve several endocrine dysfunctions. Herein, we report two cases of isolated adrenocorticotropic hormone (ACTH) deficiency induced by nivolumab for the treatment of metastatic malignant melanoma. Case 1 was a 39-year-old man and Case 2 was a 50-year-old woman, both of whom presented with progressive melanoma. After 13 courses of nivolumab administration, both cases were diagnosed with adrenal insufficiency. Despite their basal serum ACTH and cortisol levels being low with little response to corticotropin-releasing hormone loading, other anterior pituitary hormone levels were preserved. Based on these endocrinological data, isolated ACTH deficiency was diagnosed. Magnetic resonance imaging showed normal pituitary glands, excluding hypophysitis. Finally, hydrocortisone replacement enabled the patients to continue nivolumab treatment. Therefore, it is important to consider isolated ACTH syndrome as a possible and potentially severe immune-related adverse event of nivolumab, even when head magnetic resonance imaging of affected cases does not show enlargement. We should not misdiagnose hidden immune-related adverse events behind general complaints of malignancies such as general malaise and appetite loss, to allow successful treatment using this beneficial immune checkpoint inhibitor.



Efficacy and safety of a 3-month dosing regimen of degarelix in Japanese patients with prostate cancer: a phase II maintenance-dose-finding study

2017-02-18

Abstract
Objective
To evaluate the efficacy and safety of degarelix 3-month depot in Japanese patients with prostate cancer.
Methods
In this Phase II, open-label, parallel-group study, 155 Japanese prostate cancer patients were randomized to treatment with degarelix administered subcutaneously at a maintenance dose of 360 or 480 mg every 84 days for 12 months, after receiving an initial dose of 240 mg. The primary endpoint was the cumulative probability of serum testosterone ≤0.5 ng/ml (Days 28–364). Secondary endpoints included percent change in serum prostate-specific antigen level and proportion of patients with prostate-specific antigen failure at Day 364. For safety, adverse events were evaluated.
Results
The cumulative probability of serum testosterone ≤0.5 ng/ml (Days 28–364) was 88.3% (95% confidence interval: 77.9–94.0%) and 97.2% (95% confidence interval: 89.4–99.3%) in the 360 and 480 mg groups, respectively. The median percent change in serum prostate-specific antigen level from baseline to Day 364 was −95.05% and −96.43% in the 360 and 480 mg groups, respectively; the proportion of patients with prostate-specific antigen failure was 2.7% and 1.3%. The most frequent adverse event was injection site reaction; however, this did not cause any patient to discontinue treatment.
Conclusions
The 3-month dosing regimen of degarelix 360/480 mg was effective and well tolerated for treatment of Japanese prostate cancer patients. The 480 mg group showed a higher cumulative castration rate than the 360 mg group; thus, 480 mg was considered to be the optimal clinical dosage for future Phase III trials.



Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma

2017-02-15

Abstract
Objective
Patients aged ≥65 years requiring surgery for soft-tissue sarcoma are a concern in an aging society. We aimed to reveal the association of clinical/geriatric factors with survival period or postoperative events in such patients who underwent surgery.
Methods
We enrolled patients aged ≥65 years who underwent surgery for localized soft-tissue sarcoma at five institutions. We retrospectively collected clinical/geriatric factors and laboratory data, and analyzed their association with outcomes using univariate and multivariate analyses.
Results
Among the 202 patients included, mean age at presentation was 73 years. Surgical margin was R0 in 139 patients (69%). The Eastern Cooperative Oncology Group performance status was ≥2 in 15 (7%). Thirty patients (15%) showed thinness (body mass index <18.49 kg/cm2). High-sensitivity–modified Glasgow prognostic score ≥1 was seen in 52 patients (26%). Multivariate analysis showed that R1 surgical margin was significantly correlated with poor sarcoma-specific survival (hazard ratio for R1 vs. R0, 3.17; P = 0.001) and event-free survival (hazard ratio for R1 vs. R0, 2.56; P < 0.001). Higher Eastern Cooperative Oncology Group performance status was significantly associated with poor sarcoma-specific survival (hazard ratio for ≥2 vs. 0 or 1, 2.15; P = 0.038), and higher sensitivity-modified Glasgow prognostic score was significantly associated with poor event-free survival (hazard ratio for ≥1 vs. 0, 1.74; P = 0.046). Severe thinness (body mass index <16.00) was a risk factor for postoperative events (odds ratio for body mass index <16.00 vs. ≥16.00, 8.15, P = 0.010).
Conclusions
Negative surgical margin was associated with better survival. Coexisting conditions had an impact on outcomes in elderly soft-tissue sarcoma patients.



Screening using the fifth vital sign in the electronic medical recording system

2017-02-15

Abstract
Purpose
To investigate the usefulness of screening for patient symptoms as the fifth vital sign using an electronic medical recording system.
Patients and methods
In the electronic medical recording system, all admitted patients received routine nurse-based assessment of discomfort (defined as any physical symptom) at every vital sign check regarding item 2 of the Support Team Assessment Schedule Japanese version (STAS-J). All cancer patients admitted to oncology units were screened at 1-week intervals. Screening-positive was defined when patients had a STAS-J score of 2 or more at least two times in a week. For all screening-positive patients, the palliative care team reviewed each patient's medical records, and provided written recommendations as needed. The primary outcomes were the proportion of screening-positive patient, and the proportion of patients deemed to need additional palliative treatment in the screening-positive patients.
Results
Of 2427 patients screened, 223 (9.1%; 95% confidence interval, 8–10%) met the screening-positive criterion. A total of 12 (5.4%; 95% confidence interval, 3–9%) of them were deemed to need additional palliative care, including six patients referred to the PCT within 1 week. In the remaining 211 screening-positive patients, 100 had received adequate palliative care, 68 had already been referred to the palliative care team and 43 had self-limiting transient discomfort.
Conclusion
This screening system was feasible but the majority of screening-positive patients did not require additional palliative care interventions.



Evaluation of community pharmacist ability to ensure the safe use of oral anticancer agents: a nationwide survey in Japan

2017-02-10

Abstract
Objectives
A recent study of community pharmacists in Canada reported that they required additional education. We conducted a survey of community pharmacists to evaluate the adequacy of education and training in oral anticancer agents in Japan.
Methods
Between May and June 2014, community pharmacists were asked to complete a questionnaire by using two different survey strategies, one online and one via postal mail.
Results
Three hundred community pharmacists responded to an online survey and 283 community pharmacists responded to a mailed survey. Only 6–10% of respondents felt that they had received adequate education in oncology or oral chemotherapy. Although 81% of Japanese pharmacists had attended at least one continuing education event related to oncology in the past 2 years, only 54% felt comfortable dispensing oral anticancer agents and only 40% felt comfortable educating patients about oral chemotherapy. In a multivariate analysis, confidence in educating patients about oral chemotherapy was associated with an understanding of chemotherapy cycles and doses (odds ratio = 4.89, 95% confidence interval [2.53–9.45]) and the number of continuing education events they had attended (odds ratio = 1.67, 95% confidence interval [1.35–2.08]).
Conclusions
This is the first report to evaluate whether community pharmacists are equipped to ensure the safe use of oral anticancer agents in Japan. The results are similar to those previously reported for Canadian pharmacists, namely a low rate of positive responses for education in oncology and oral chemotherapy, demonstrating a similar need for additional education and training in oral chemotherapy.



Lymphovascular invasion predicts poor prognosis in high-grade pT1 bladder cancer patients who underwent transurethral resection in one piece

2017-02-10

Abstract
Background
Lymphovascular invasion (LVI) in high-grade clinical T1 bladder cancer is usually considered a poor prognostic factor, but it is often difficult to achieve correct staging of T1 bladder cancer and diagnose the presence of LVI because of the inadequacy of conventional transurethral resection specimens. The aims of this study were to evaluate the prognostic value of LVI in patients with correctly staged high-grade pathological T1 (pT1) bladder cancer who initially underwent transurethral resection in one piece (TURBO).
Methods
Eighty-six high-grade pT1 bladder cancer patients who underwent TURBO were enrolled. Risk of tumor understaging was avoided by examining the vertical resection margin of the TURBO specimen. Immunohistochemical staining using D2-40 and CD31 was performed to confirm LVI. We examined the association of LVI with other clinicopathological factors and the impact of LVI on progression-free survival and cancer-specific survival.
Results
The median follow-up period was 49 months (range, 6−142). In all patients, the tumors were accurately staged as pT1 at initial TURBO. LVI was detected in 15 patients (17%) and was significantly associated with tumor growth pattern (P = 0.001). Multivariate analysis identified LVI as the only independent predictor for reduced progression-free survival (HR, 4.48; 95% CI, 1.45−13.90; P = 0.009) and cancer-specific survival (HR, 4.35; 95% CI, 1.17−16.24; P = 0.029).
Conclusions
The presence of LVI in TURBO specimens independently predicts poor clinical outcomes in patients with high-grade pT1 bladder cancer. This information may help urologists to counsel their patients when deciding whether to choose a bladder-preserving strategy or radical cystectomy.



Smoking effect on oncological outcome among men with prostate cancer after radical prostatectomy

2017-02-10

Abstract
Objective
To analyze the association between smoking and oncological outcome after radical prostatectomy in patients with prostate cancer.
Methods
This study included men who underwent radical prostatectomy between 2003 and 2013. The association of clinicopathological factors with smoking status and the prognostic significance of clinicopathological factors and smoking status on biochemical recurrence (BCR) were evaluated.
Results
Of the 1165 included patients, 226 (19.4%) were current smokers and 939 (80.6%) were nonsmokers. The median observation period was 39 months (interquartile range, 15–75 months). Current smokers were younger than nonsmokers and had higher PSA levels, higher biopsy and pathological Gleason scores, and more frequent lymph-node involvement than nonsmokers. Pathological Gleason score, extracapsular extension, seminal vesicle invasion, positive surgical margin, lymph-node involvement, and current smoking (hazard ratio [95% confidence interval]; 1.31 [1.00–1.72], P = 0.046) were identified as significant risk factors of BCR on univariate analysis. However, smoking status was not an independent predictive marker on multivariate analysis.
Conclusions
Current smokers had adverse clinicopathological characteristics including high PSA level, high Gleason score, and lymph node involvement, suggesting that smoking promoted the progression of prostate cancer.






Pharmacokinetics of initial full and subsequent reduced doses of S-1 in patients with locally advanced head and neck cancer—effect of renal insufficiency

2017-02-04

Abstract
Background
S-1 is a combination of tegafur [metabolized to 5-fluorouracil (5-FU)] with the modulators gimeracil (5-chloro-2,4-dihydroxypyridine) and oteracil potassium. 5-Chloro-2,4-dihydroxypyridine maintains plasma 5-FU concentrations by inhibiting dihydropyrimidine dehydrogenase, a pyrimidine catabolism enzyme that degrades 5-FU. As 50% of 5-chloro-2,4-dihydroxypyridine is excreted in urine, renal insufficiency may increase its blood level, increasing 5-FU concentrations. We investigated whether special dose modification is needed in the presence of renal insufficiency.
Objective
We compared steady state pharmacokinetics of 5-FU for the initial S-1 dose and reduced doses in patients with head and neck cancer requiring dose reduction due to renal and non-renal toxicities.
Methods
Chemoradiotherapy with S-1 and cisplatin was administered every 5 weeks for two courses with a radiation dose totaling 70 Gy over 33–35 fractions. Two additional courses of adjuvant chemotherapy were administered in the case of an objective response. The S-1 and/or cisplatin dose was reduced in response to renal, hematologic or other toxicities. The primary endpoint was the change in area under the plasma concentration-versus-time curve from time 0–10 hours (5-FU AUCss 0–10) between the initial and reduced S-1 doses.
Results
Although the mean 5-FU levels in patients with non-renal toxicities significantly decreased between the full and reduced dose, the full-dose and reduced-dose mean maximum 5-FU plasma concentrations at steady state (Css max) and AUCss 0–10 in patients with renal insufficiency were similar.
Conclusions
Standard S-1 dose reduction for renal toxicity did not result in a significant decrease in 5-FU levels at steady state. A greater reduction to lower plasma 5-chloro-2,4-dihydroxypyridine may be necessary in patients with renal insufficiency.



Progress of liver resection for hepatocellular carcinoma in Taiwan

2017-02-04

Abstract
Taiwan is a well-known endemic area of hepatitis B. Hepatocellular carcinoma (HCC) has consistently been the first or second highest cause of cancer death over the past 20 years. This review article describes the progress of liver resection for HCC in Taiwan in the past half century. The mortality rate for HCC resection was 15–30% in Taiwan in the 1970s. The rate decreased to 8–12% in the early 1990s, and it declined to <1–3% recently. The development of new operative instruments, and surgical techniques, increased knowledge of liver anatomy and pathophysiology after hepatectomy, and more precise patient selection have contributed to this improvement. The use of intermittent hepatic inflow blood occlusion, a restrictive blood transfusion policy and intraoperative ultrasonography, have also led to substantial improvements in resectability and safety for HCC resection in Taiwan. Advances in non-operative modalities for HCC treatment have also helped to improve long-term outcomes of HCC resection. Technical innovations have allowed the application of complex procedures such as mesohepatectomy, unroofing hepatectomy, major portal vein thrombectomy, hepatic vein reconstruction in resection of the cranial part with preservation of the caudal part of the liver, and inferior vena cava and right atrium tumor thrombectomy under cardiopulmonary bypass. In selected patients, including patients with end-stage renal failure, renal graft recipients, patients with portal hypertension, hypersplenic thrombocytopenia and/or associated gastroesophageal varices, octogenarian, ruptured HCC, recurrent HCC and metastatic HCC can also be resected with satisfactory survival benefits. We conclude that the results of liver resection for HCC in Taiwan are improving. The indications for HCC resection continue extending with lower the surgical risks and increasing the long-term survival rate.



Characteristics of cancer patients who died by suicide in the Tokyo metropolitan area

2017-02-02

Abstract
The purpose of this study was to investigate the sociodemographic characteristics of cancer patients who died by suicide in comparison with cancer-free cases. Suicide data from the Tokyo Medical Examiner's Office from 2009 to 2013 were extracted retrospectively. A total of 503 (5.1%) out of 9841 people who committed suicide had cancer; age ranged from 26 to 97 years. The cancer patients were significantly older than the cancer-free cases. There were significantly more cancer patients with cohabiters than cancer-free cases with cohabiters. Only half of young to middle-aged subjects had a job in both groups. There were significantly more cancer patients who lived on pensions and welfare assistance, and less cancer patients who drink or smoke than those without cancer. Given the high incidence of suicide in elderly cancer patients, healthcare professionals should pay attention for risk even in cancer patients who have cohabiters, benefit from a pension, and do not drink or smoke.



First-line bevacizumab plus paclitaxel in Japanese patients with HER2-negative metastatic breast cancer: subgroup results from the randomized Phase III MERiDiAN trial

2017-02-02

Abstract
Background
In the double-blind placebo-controlled randomized Phase III MERiDiAN trial (ClinicalTrials.gov NCT01663727), adding bevacizumab to paclitaxel for HER2-negative metastatic breast cancer (mBC) significantly improved progression-free survival (PFS; stratified hazard ratio [HR] 0.68, 99% confidence interval [CI], 0.51–0.91). We assessed the efficacy and tolerability of first-line bevacizumab–paclitaxel in the subset of Japanese patients in MERiDiAN.
Methods
Eligible patients had HER2-negative mBC previously untreated with chemotherapy. Plasma vascular endothelial growth factor (VEGF)-A was measured before randomization to paclitaxel 90 mg/m2 on Days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on Days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were: baseline plasma VEGF-A level, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary endpoints were investigator-assessed PFS in the intent-to-treat (ITT) population and in the subgroup with high plasma VEGF-A. This exploratory analysis evaluated efficacy and safety in the subpopulation treated in Japanese centers.
Results
Of 481 patients randomized in MERiDiAN, 54 (11%) were Japanese. The stratified PFS HR in the Japanese subgroup was 0.64 (95% CI, 0.29–1.40). Median PFS was 9.2 months with placebo–paclitaxel (n = 30) versus 12.7 months with bevacizumab–paclitaxel (n = 24). Bevacizumab was associated with increased incidences of Grade ≥3 neutropenia, peripheral sensory neuropathy and hypertension, but there was no Grade ≥3 proteinuria, bleeding or gastrointestinal perforation.
Conclusions
Bevacizumab–paclitaxel efficacy in Japanese patients was consistent with the MERiDiAN ITT population. No new safety signals were seen and tolerability was consistent with previous experience.